f 

rTTri^H 

1 

ifl'lUxJl  ftlCl  I  ;  ' 


khV 


TO',: 
til 


p 


'111 


tV'r^  ■' 


X 


Nortli  (Earoltna  BtuU 


This  book  was  presented  by 

Z.P.rAe+cal-S- 

QH55I 
C5 


5rty  of 

OF  AGRICULTURE 
logy  and  tiitomoiogy- 


IW*«.^MU 


-  •^»^'   ''"in.  - 


Property  of 

N.  C.  COLLEGE  OF  AGRICULTURE 
Department  of  Zoology  and  Entomolo^ 


No.. 


^w«iB»*WwanrftBy>irM  mw  *nwiMMilhi 


J 


«^43 1 

This  book  may  be  kept  out  TWO  WEEKS 
ONLY,  and  is  subject  to  a  fine  of  FIVE 
CENTS  a  day  thereafter.  It  is  due  on  the 
day   indicated   below: 


2lMaM7S 
27Jul48t 


i 


Mar  5.  ■ 
BJanSdQ 

5iul55? 

7Apr'60' 

NOV  2  1  m 


5M— D-45— Form  3 


SENESCENCE  AND   REJUVENESCENCE 


THE  UNIVERSITY  OF  CHICAGO  PRESS 
CHICAGO,  ILLINOIS 


AgrtttB 
THE  CAMBRIDGE  UNIVERSITY  PRESS 

LONDON  AND  EDINBURGH 

THE  MARUZEN-KABUSHIKI-KAISHA 

TOKYO,  OSAKA,  KYOTO 

KARL  W.  HIERSEMANN 

LEIPZIG 

THE  BAKER  &  TAYLOR  COMPANY 

NEW  TORK 


SENESCENCE 

AND 

REJUVENESCENCE 


By 
CHARLES   MANNING  CHILD 

Of  the  Department  of  Zoology 
The  Uni-versity  of  Chicago 


THE  UNIVERSITY  OF  CHICAGO  PRESS 
CHICAGO,  ILLINOIS 


Copyright  1915  By 
The  University  of  Chicago 


All  Rights  Reserved 


Published  October  IQ15 


Composed  and  Printed  By 

The  University  of  Chicago  Press 

Chicago.  Illinois,  U.S.A. 


PREFACE 

The  following  study  of  senescence  and  rejuvenescence  is  pri- 
marily a  register  of  progress  along  certain  lines  of  a  research  program 
on  which  I  have  been  engaged  during  the  last  fifteen  years.  This 
program  began  with  the  attempt  to  analyze  experimentally  the 
simpler  reproductive  processes,  but  it  at  once  became  evident  that 
the  whole  problem  of  the  organic  individual,  its  origin,  development, 
physiological  character,  and  limiting  factors,  was  involved.  In 
the  study  of  the  organic  individual  the  importance  of  the  physio- 
logical age  changes  soon  became  apparent  and  it  was  found  neces- 
sary to  devote  considerable  time  to  their  analysis,  for  the  origin  of 
new  individuals  by  reproduction  is  in  many  cases  very  closely 
associated  with  physiological  aging.  And  since  the  conclusions 
reached  concerning  the  age  cycle  finally  attained  a  definite,  positive 
form,  differing  to  some  extent  from  commonly  accepted  \'iews, 
but  seeming  to  throw  some  light  upon  various  other  biological 
problems,  it  has  seemed  desirable  to  attempt  a  general  considera- 
tion and  synthesis  of  the  subject  of  age  changes  from  the  point  of 
view  which  has  grown  out  of  the  research  program  mentioned 
above. 

It  will  appear  clearly  in  the  following  pages  that  the  problems 
of  individuation,  reproduction,  and  age  are  all  closely  connected. 
For  that  reason  it  has  been  necessary  to  devote  a  chapter — chap,  ix 
— to  the  problem  of  individuation  and  reproduction.  This  chapter 
is  merely  a  brief  statement  of  some  of  the  more  important  evidence 
and  the  conclusions  reached  concerning  the  nature  of  the  organic 
individual,  a  full  consideration  of  the  subject  being  left  to  another 
time. 

About  half  the  book  is  a  presentation  of  results  of  my  own 
investigations  and  the  larger  part  of  these  have  not  been  published 
elsewhere.  Consequently  the  book  stands  as  a  record  of  research 
as  well  as  an  attempt  at  a  general  survey.  No  attempt  has  been 
made  to  present  a  complete  bibHography  of  the  subject  of  age.  The 
references  are  to  a  large  extent  intended  to  serve  rather  as  guides 
or  aids  in  obtaining  further  knowledge  of  the  literature  than  as  an 

V 


VI  PREFACE 

exhaustive  bibliography.  The  matter  of  selection  has  often  been 
a  difficult  one  and  doubtless  references  have  been  omitted  which 
should  have  been  included.  For  such  errors  of  judgment  or  of 
ignorance  I  must  accept  the  full  responsibihty. 

At  various  points  in  the  book  it  has  seemed  necessary  to  extend 
the  consideration  into  fields  more  or  less  remote  from  those  with 
which  I  am  most  famihar.  I  must  frankly  acknowledge,  however, 
that  some  of  these  ventures  into  other  fields  have  been  attended  by 
the  feeling  that  discretion  would  perhaps  have  been  the  better  part 
of  valor,  for  any  venture  very  far  outside  one's  own  little  garden  plot 
of  scientific  thought  is  likely  to  be  attended  by  a  very  decided  f  eehng 
of  strangeness;  one  realizes  that  one  is  not  at  home.  Nevertheless 
such  ventures  are  necessary  if  different  lines  of  investigation  and 
thought  are  to  be  co-ordinated  and  synthesized  into  a  harmonious 
whole.  I  can  only  hope  that  in  this  particular  case  the  excursions 
into  neighboring  gardens  and  fields  have  not  been  wholly  fruitless 
or  mistaken.  As  regards  actual  errors  of  statement  or  reference 
and  other  similar  matters  which  may  have  escaped  correction,  I 
can  only  plead  human  fallibility. 

It  has  been  necessary,  particularly  in  those  chapters  which  are 
concerned  with  the  various  reproductive  processes  and  with  the 
morphology  of  the  gametic  cells,  to  use  figures  from  various  other 
authors  and  I  wish  to  acknowledge  my  obligations  for  such  figures. 
Figs.  I02,  103,  104,  105,  106,  107,  A-C,  108,  125,  128,  132,  133,  134, 
135,  136,  137,  138,  139,  141,  A-E,  are  reproduced  from  A  Text- 
book of  Botany  by  Coulter,  Barnes,  and  Cowles,  by  permission  of 
the  American  Book  Company,  publishers,  and  Dr.  Coulter,  the 
senior  author.  I  am  greatly  indebted  both  to  the  publishers  and 
to  Dr.  Coulter  for  permission  to  use  these  figures  of  characteristic 
morphological  and  reproductive  features  of  plant  life.  Figs.  11 1 
and  112  are  reproductions  in  slightly  modified  form  from  Minot's 
T/ie  Problem  of  Age,  Growth  and  Death,  by  permission  of  the  pub- 
lishers, Messrs.  G.  P.  Putnam's  Sons.  For  other  figures  which  are 
not  original  acknowledgment  is  made  in  the  legends,  and  since  it 
is  often  highly  desirable  to  know,  not  only  the  author  of  a  particular 
figure,  but  the  publication  in  which  it  originally  appeared,  a  refer- 
ence number,  as  well  as  the  author's  name,  is  given  and  the  full 


PREFACE  vii 

reference  is  included  in  the  list  at  the  end  of  the  chapter  in  which 
the  figure  appears. 

For  permission  to  cite  unpublished  data  I  am  indebted  to 
Dr.  S.  Tashiro,  of  the  Department  of  Biochemistry,  to  Miss  L.  H. 
Hyman,  of  the  Department  of  Zoology,  and  to  Mr.  M.  M.  Wells, 
formerly  of  the  Department  of  Zoology,  of  the  University  of  Chicago. 
For  the  redrawing  of  all  figures  from  other  authors  and  for  a  num- 
ber of  original  drawings  from  preparations  I  am  indebted  to  Mr. 
Kenji  Toda,  the  artist  of  the  Department  of  Zoology,  and  I  wish  to 
express  my  appreciation  of  his  work.  For  the  reading  of  parts  of 
the  manuscript  and  proofs  and  for  various  suggestions  and  criti- 
cisms my  thanks  are  due  to  my  colleagues.  Dr.  A.  P.  Mathews 
and  Dr.  C.  J.  Herrick.  To  my  wife,  Lydia  Van  Meter  Child,  I 
am  deeply  indebted  for  her  unfailing  co-operation  and  assistance 
in  the  preparation  of  the  manuscript  and  proofs.  And,  lastly,  I 
wish  to  express  my  appreciation  of  the  manner  in  which  the  Uni- 
versity of  Chicago  Press  has  done  its  part  as  publisher. 

C.  M.  Child 
Hull  Zoological  Laboratory 
University  of  Chicago 
May,  1915 


TABLE  OF  CONTENTS 
Introduction  .......... 

PART  I.     THE  PROBLEM  OF  ORGANIC  CONSTITUTION 
Chapter 

I.    Various  Theories  of  the  Organism 


Pace 
I 


Neo-vitalistic  Theory;  Corpuscular  Theories;  Chemical  Theory; 
Physico-chemical  Theory;  The  Colloid  Substratum  of  the  Organism; 
The  Relation  between  Structure  and  Function;    References. 


II.    The  Life  Cycle 


34 


Growth  and  Reduction:  Definitions  of  Growth  and  Reduction,  The 
Nature  of  Growth  and  Reduction;  Differentiation  and  Dedifferentia- 
tion:  Differentiation,  Dedifferentiation;  The  Basis  of  Senescence  and 
Rejuvenescence;  References. 

PART  II.     AN  EXPERIMENTAL  STUDY  OF  PHYSIOLOGICAL  SENES- 
CENCE AND  REJUVENESCENCE  IN  THE  LOWER  ANIMALS 

III.  The  Problem  and  Methods  of  Investigation      ....       63 

The  Nature  of  the  Problem;  Susceptibility  in  Relation  to  Rate  of  Metab- 
olism; The  Direct  Method;  The  Indirect  Method;  Other  Methods; 
References. 

IV.  Age  Differences  in  Susceptibility  in  the  Lower  Animals  .       92 

The  E.xperimental  Material;  Age  Differences  in  Susceptibilty  in  Pla- 
naria  maciilata;  Age  Differences  in  Susceptibility  in  Planar'ui 
dorolocephala;  Age  Differences  in  Susceptibility  in  Other  Forms; 
Conclusion;    References. 

V.    The  Reconstitution  of  Isolated  Pieces  in  Rel.\tion  to  Re- 
juvenescence IN  Planar ia  and  Other  Forms 103 

The  Reconstitution  of  Pieces  in  Planaria;  Changes  in  Susceptibility 
during  the  Reconstitution  of  Pieces;  The  Increase  in  Susceptibility  in 
Relation  to  the  Degree  of  Reconstitution;  The  Susceptibility  of  .\ni- 
mals  Resulting  from  E.xperimental  Reproduction  and  Se.xually  Pro- 
duced Animals;    Repeated  Reconstitution;    References. 

VI.    The  Relation  between  Agamic  Reproduction  and  Reju- 
venescence IN  the  Lower  Animals 122 

The  Process  of  Agamic  Reproduction  in  Planaria  dorolocephala  and  Re- 
lated Forms;  The  Occurrence  of  Rejuvenescence  in  .\gamic  Reproduc- 
tion in  Planaria  dorolocephala  and  P.  maculala;  .-\gamic  Reproduction 
and  Rejuvenescence  in  P.  velala;  Agamic  Reproduction  and  Re- 
juvenescence in  Slenoslomum  and  Certain  Annelids;  The  Relation  be- 
tween Agamic  Reproduction  and  Rejuvenescence  in  Protozoa;  .\gamic 
Reproduction  and  Rejuvenescence  in  Coelenterates;    References. 

ix 


X  TABLE  OF  CONTENTS 

Chapter  Page 

VII.    The  Role  of  Nutrition  in  Senescence  and  Rejuvenescence 

IN  Planaria 155 

Reduction  by  Starvation  in  Planaria;  Changes  in  Susceptibility  during 
Starvation  in  P.  dorotocephala  and  P.  vclata;  The  Production 
of  Carbon  Dioxide  by  Starved  Animals;  The  Rate  of  Decrease 
in  Size  during  Starvation;  The  Capacity  of  Starved  Animals  for  Accli- 
mation; Partial  Starvation  in  Relation  to  Senescence;  The  Character 
of  Nutrition  in  Relation  to  the  Age  Cycle;  References. 

Vm.    Senescence  and  Rejuvenescence  in  the  Light  of  the  Pre- 
ceding Experiments 178 

Review  and  Analysis  of  the  Experimental  Data;  The  Nature  of  Senes- 
cence and  Rejuvenescence;  Periodicity  in  Organisms  in  Relation  to 
the  Age  Cycle;  Senescence  and  Rejuvenescence  in  Evolution; 
References. 


PART  III.     INDIVIDUATION  AND   REPRODUCTION  IN  RELATION  TO 

THE  AGE  CYCLE 

IX.    Individuation  and  Reproduction  in  Organisms   .     .     .     .     199 

The  Problem;  The  Axial  Gradient;  Dominance  and  Subordination  of 
Parts  in  Relation  to  the  Axial  Gradients;  The  Nature  and  Limits  of 
Dominance;  Degrees  of  Individuation;  Physiological  Isolation  and 
Agamic  Reproduction;   References. 

X.    The  Age  Cycle  in  Plants  and  the  Lower  Animals     .     .     237 

Individuation  and  Agamic  Reproduction  in  the  Life  Cycle  of  Plants; 
The  Vegetative  Life  of  Plants  in  Relation  to  Senescence;  The  Occur- 
rence of  Dedifferentiation  and  Rejuvenescence  in  Plant  Cells;  The  Rela- 
tion of  the  Different  Forms  of  Agamic  Reproduction  in  Plants  to  the 
Age  Cycle;  Individuation,  Agamic  Reproduction,  and  the  Age  Cycle 
in  the  Lower  Animals;  Senescence  as  a  Condition  of  Reproduction  and 
Rejuvenescence;  Conclusion;  References. 

XI.    Senescence  in  the  Higher  Animals  and  Man     ....     266 

Individuation  and  Reproduction  in  the  Higher  Forms  in  Relation  to 
the  Age  Cycle;  The  Process  of  Senescence  in  the  Higher  Forms;  The 
Rate  of  Metabolism;  The  Rate  of  Growth;  Nutrition,  Growth,  and 
Senescence;  Changes  in  Water-Content  and  Chemical  Constitution; 
The  Morphological  Changes;   Conclusion;   References. 

XII.    Rejuvenescence  AND  Death  IN  THE  Higher  Animals  AND  Man    293 

Rejuvenescence  in  the  Life  History;  Length  of  Life  and  Death  from 
Old  Age;  Some  Theories  of  Length  of  Life;  Conclusion;  References. 


TABLE  OF  CONTENTS  xi 

PART  IV.     GAMETIC  REPRODUCTION  IN  RELATION 
TO  THE  AGE  CYCLE 

Ch.^PTER  p^j.g 

XIII.  Origin  axd  jMorphological  and  Physiological  Coxditiox 

OF  THE  Gametes  in  Plants  and  Aniivl\ls 315 

The  Theoretical  Significance  of  Gametic  Origin;  The  Origin  of  the 
Gametes  in  Plants;  The  Origin  of  the  Gametes  in  Animals;  The  Mor- 
phological Condition  of  the  Gametes;  The  Physiological  Condition  of 
the  Gametes;  The  Significance  of  ^laturation;  Conclusion;  Refer- 
ences. 

XIV.  Conditions  of  Gamete  Formation  in  Plants  and  Anbuls    364 

Conditions  of  Gamete  Formation  in  the  Algae  and  Fungi;  Conditions  of 
Gamete  Formation  in  Mosses  and  Ferns;  Conditions  of  Gamete  Forma- 
tion in  the  Seed  Plants;  Conditions  of  Conjugation  in  the  Protozoa; 
Conditions  of  Gamete  Formation  in  the  Multicellular  Animals; 
Parthenogenesis  and  Zygogenesis;    Conclusion;    References. 

XV.    Rejuvenescence  IN  Embryonic  AND  Larval  Development  403 

The  Effect  of  Fertilization;  Parthenogenesis;  The  Experimental  Ini- 
tiation of  Development;  Oxygen  Consumption  and  Heat  Production 
during  Early  Stages  of  Development;  Changes  in  Susceptibility  dur- 
ing Early  Stages;  The  IMorphological  Changes  during  Early  Develop- 
ment; Larval  Stages  and  Metamorphosis;  Embryonic  Development  in 
Plants;  The  Degree  of  Rejuvenescence  in  Gametic  and  Agamic  Repro- 
duction; Conclusion;  References. 


PART  V.    THEORETICAL  AND  CRITICAL 

XVI.  Some  Theories  of  Senescence  and  Rejuvenescence     .     .     433 

Senescence  as  a  Special  or  Incidental  Feature  of  Life;  Senescence  as  a 
Result  of  Organic  Constitution;  The  Conception  of  Growth  as  an  Auto- 
catalytic  Reaction  and  the  Resulting  Theory  of  Senescence;  Refer- 
ences. 

XVII.  Some  General  Conclusions  and  Their  Significance  for 
Biological  Problems 450 

Index 469 


INTRODUCTION 

The  succession  of  generations  and  the  repetition  of  the  life  cycle 
in  the  individual  are  the  two  great  facts  about  which  biological 
thought  centers.  The  problems  of  reproduction,  growth,  develop- 
ment, inheritance,  and  evolution,  as  well  as  many  other  special 
problems,  are  concerned  with  one  aspect  or  another  of  these  funda- 
mental characteristics  of  life.  Life  as  we  know  it  exists  only  in  the 
form  of  individuals  of  various  degrees  and  kinds  which  pass  through 
a  definite  series  of  changes  and  give  rise  to  other  individuals,  and 
these  in  turn  repeat  the  process  more  or  less  exactly. 

At  the  beginning  of  a  new  generation  the  size  of  the  organism  is 
usually  only  a  fraction  of  that  to  which  it  finally  attains.  Various 
substances  are  taken  up  by  the  organism  as  food  and  transformed 
in  part  into  the  energy  of  its  activity  and  in  part  into  the  material 
substratum  in  which  the  dynamic  activities  occur.  Under  the 
usual  conditions  this  material  substratum  which  constitutes  the 
visible  organism  increases  in  amount  or  grows  during  a  large  part 
of  the  life  of  the  organism. 

In  all  except  perhaps  the  very  simplest  organisms  another  series 
of  changes  occurs  which  we  call  morphogenesis  or  differentiation. 
Localized  differences  in  constitution,  form,  or  structure  appear, 
and  we  say  that  the  organism  undergoes  dift'erentiation.  Under 
natural  conditions  this  process  of  differentiation  is  very  commonly 
associated  with  growth,  but  the  fact  that  it  may  occur  in  the  com- 
plete absence  of  growth  shows  that  the  association  is  by  no  means 
a  necessary  one. 

Sooner  or  later  and  in  one  way  or  another  the  organism  gives 
rise  to  one  or  more  new  organisms,  which  like  their  parent  are  at 
first  relatively  small  and  simple,  and  like  it  also  undergo  a  process 
of  growth  and  differentiation.  This  is  reproduction.  In  some  of 
the  simpler  forms  of  reproduction  the  parent  organism  divides 
into  two  or  more  parts  which  constitute  the  new  generation,  and 
there  is  nothing  which  corresponds  to  death  in  the  usual  sense. 
The  old  individuaHty  is  replaced  by  new  individualities,  but  nothing 


D.   H.  HILL  LIBRARY 

North  Carolina  State  College 


2  SENESCENCE  AND  REJUVENESCENCE 

is  left  behind.  In  such  cases  there  is,  as  Weismann  has  aptly  put 
it,  no  death  because  there  is  no  corpse. 

We  see,  however,  that  in  certain  other  forms  of  reproduction,  as 
in  various  types  of  sporulation  in  plants  and  budding  in  lower 
animals,  and  in  sexual  reproduction  also  if  we  take  the  facts  at 
their  face  value  without  reference  to  the  germ-plasm  theory,  only 
a  circumscribed  part  of  the  parent  organism  is  directly  involved  in 
reproduction.  In  such  cases  the  parent  organism  either  remains 
alive  for  a  longer  or  shorter  time,  perhaps  with  periodic  or  con- 
tinuous reproduction,  or  it  dies  almost  at  once.  In  short,  death 
of  the  non-reproductive  or  somatic  parts  of  the  organism  is  ap- 
parently the  final  result  in  at  least  most  of  these  cases. 

In  the  higher  animals  which  reproduce  only  sexually,  and  in  at 
least  many  of  the  higher  plants,  certain  physiological  and  morpho- 
logical changes  accompany  growth  and  development  of  the  somatic 
parts.  The  rate  of  growth  decreases,  in  many  cases  irritability 
and  the  rate  of  metabolism  have  also  been  found  to  decrease,  a 
relative  and  later  an  absolute  decrease  in  the  percentage  of  water 
occurs,  the  structural  elements  become  less  plastic  and  in  some 
cases  undergo  more  or  less  atrophy  in  later  stages,  and  the  organism 
in  general  appears  to  be  gradually  losing  its  vigor.  In  many  plants 
these  changes  occur  rapidly  in  certain  parts  and  may  be  long,  perhaps 
indefinitely,  delayed  in  others,  and  it  will  be  shown  in  Part  III 
that  the  same  is  true  for  many  of  the  lower  animals;  but  in  the 
higher  animals  the  whole  of  the  body  is  apparently  involved,  though 
even  here  the  facts  indicate  that  these  changes  may  occur  more 
rapidly  in  one  part  or  another  according  to  various  conditions. 

These  changes,  which  constitute  a  gradual  deterioration  of  the 
organism,  a  gradual  decrease  in  the  intensity  of  its  living,  are  com- 
monly designated  as  aging  or  senescence.  The  question  whether 
certain  changes  are  properly  to  be  regarded  as  senescence  or  not 
may  often  be  raised  with  respect  to  particular  cases,  but  in  general 
there  can  be  no  doubt  that  in  at  least  many  organisms  a  process 
of  senescence  does  occur:  the  organism  grows  old.  Moreover, 
there  is  no  doubt  that  in  at  least  many  forms  this  process  of  senes- 
cence leads  to  the  cessation  of  the  processes  of  life,  i.e.,  to  what 
we  call  death. 


INTRODUCTION  3 

The  occurrence  of  senescence  in  the  organic  world  raises  many 
questions  of  great  interest  and  importance,  not  only  for  the  scientist, 
but  in  certain  aspects  for  the  human  race  in  general.  How  do  young 
and  old  organisms  differ  from  each  other,  and  what  is  the  nature 
of  senescence  ?  Is  it  a  feature  of  the  fundamental  processes  of  life 
or  the  result  of  incidental  conditions  ?  Does  it  occur  in  all  organ- 
isms or  only  in  the  more  complex,  more  highly  differentiated  forms  ? 
Does  it  inevitably  lead  sooner  or  later  to  death,  or  is  a  rejuvenes- 
cence of  old  organisms  or  parts  possible  ?  Is  the  process  of  senes- 
cence in  a  given  organism  always  of  the  same  character,  or  does  it 
depend  upon  the  environmental  conditions  ?  Is  the  rate  of  senes- 
cence always  the  same  in  a  particular  species,  or  does  it  differ  in 
different  individuals  according  to  the  action  of  internal  or  external 
factors.  Many  of  these  questions  can  be  summed  up  in  the  one, 
Can  we  control  senescence  ? 

In  nature  the  organism  resulting  from  the  union  of  the  two 
sexual  cells  is  young.  This  fact  raises  another  series  of  questions. 
Does  rejuvenescence  occur  somewhere  in  the  course  of  sexual  re- 
production, or  does  the  germ  plasm  from  which  the  sex  cells  arise 
not  grow  old  ?  Are  the  organisms  which  result  from  asexual  re- 
production also  young,  or  is  sexual  reproduction  the  only  process 
which  gives  rise  to  young  organisms?  If  rejuvenescence  occurs, 
upon  what  does  its  occurrence  depend  and  what  is  its  nature  ? 
Does  it  occur  in  all  organisms,  or  only  in  certain  of  them  ?  Is  com- 
plete rejuvenescence  possible,  or  is  the  species  and  the  organic  world 
in  general  undergoing  a  senescence  which  will  lead  to  extinction  ? 

These  are  a  few  of  the  most  important  questions  w'hich  the 
occurrence  of  senescence  and  the  processes  of  reproduction  lead  us 
to  ask.  In  the  following  chapters  these  and  some  other  questions 
will  be  considered  in  the  light  of  the  experimental  and  observational 
evidence  which  we  possess.  To  some  of  these  questions  we  shall 
be  able  to  give  a  definite  answer,  to  some  others  the  answer  must 
be  provisional,  and  some  we  must  leave  open  for  the  future  to 
answer,  though  even  here  we  can  indicate  the  direction  in  which 
the  facts  point. 

The  problem  of  senescence  has  been  discussed  many  times  in 
the  history  of  biology,  and  many  hypotheses  as  to  its  nature  have 


4  SENESCENCE  AND  REJUVENESCENCE 

been  elaborated.  Unfortunately  by  far  the  greater  part  of  the 
work  along  this  line  has  dealt  chiefly  with  the  process  of  senescence 
as  it  appears  in  man  and  the  higher  mammals.  Only  now  and 
then  has  an  attempt  been  made  even  to  formulate  a  general  theory 
of  senescence,  and  analytic  investigation  of  senescence  in  the 
lower  organisms  has  scarcely  been  attempted.  This  limitation  in 
the  investigation  of  the  problem  of  senescence  is  due  to  the  fact 
that  in  the  past  interest  in  the  problem  has  been  very  largely  con- 
fined to  the  medical  profession. 

It  is  of  course  true  that  we  are  most  familiar  with  the  phenomena 
of  senescence  in  man  and  other  mammals,  the  most  complex  of  all 
organisms.  But  man  is  a  member  of  the  organic  world  and  a  prod- 
uct of  evolution,  and,  as  we  have  traced  the  development  of  his 
structure  from  lower  forms,  so  we  must  look  to  the  lower  forms  for 
adequate  knowledge  of  his  physiological  processes.  Before  we 
can  understand  senescence  in  man  we  must  determine  what  it  is  in 
its  simplest  terms. 

The  present  book  finds  its  chief  reason  for  existence  in  the  fact 
that  it  has  been  possible  with  the  aid  of  certain  experimental 
methods  of  investigation  to  obtain  some  definite  knowledge  con- 
cerning the  processes  of  senescence  and  rejuvenescence  in  the  lower 
animals.  The  facts  discovered  aft'ord,  as  I  believe,  a  basis  for  the 
further  investigation  of  senescence  and  rejuvenescence  in  general, 
and  for  an  analytic  consideration  and  interpretation  of  various 
phenomena  in  plants  and  animals  which  are  more  or  less  closely 
associated  with  these  processes.  Since  the  most  important  result 
of  these  investigations  is,  in  my  opinion,  the  demonstration  of  the 
occurrence  of  rejuvenescence  quite  independently  of  sexual  repro- 
duction, the  book  differs  to  some  extent  from  most  previous 
studies  of  senescence  in  that  it  attempts  to  show  that  in  the 
organic  world  in  general  rejuvenescence  is  just  as  fundamental 
and  important  a  process  as  senescence.  In  the  higher  forms 
the  possibihties  of  rejuvenescence  are  apparently  very  narrowly 
limited,  but  in  the  simpler  organisms  it  is  a  characteristic  feature 
of  life,  and  the  nature  of  the  process  here  enables  us  to  under- 
stand more  clearly  certain  changes  which  occur  in  the  higher 
forms. 


INTRODUCTION  5 

My  investigation  of  senescence  and  rejuvenescence  has  been 
closely  connected  with  an  attempt  to  determine  the  physiological 
nature  of  the  reproductive  processes  in  organisms,  and  I  believe 
that  some  such  conception  of  senescence  and  rejuvenescence  as 
that  presented  here  is  essential  for  the  physiological  analysis  of 
reproduction,  since  senescence,  reproduction,  and  rejuvenescence 
are  very  closely  connected.  But  while  some  discussion  of  the 
nature  of  various  reproductive  processes  will  be  necessary  in  the 
course  of  the  present  study,  a  full  consideration  of  the  problem  of 
reproduction  is  postponed  to  another  time. 

Our  conception  of  the  nature  of  these  various  processes,  growth, 
differentiation,  senescence,  reproduction,  and  rejuvenescence,  must 
depend  upon  our  conception  of  the  organism.  It  seems  necessary, 
therefore,  to  consider  briefly  in  certain  of  its  aspects  the  problem 
of  the  constitution  of  the  organism  by  way  of  clearing  the  ground 
for  consideration  of  the  particular  features  of  organic  constitution 
which  form  the  subject  of  the  book. 


PART  I 
THE  PROBLEM  OF  ORGANIC  CONSTITUTION 


*^ 


CHAPTER  I 

VARIOUS  THEORIES  OF  THE  ORGANISM 

NEO-VITALISTIC  THEORY 

To  the  primitive  man  all  the  phenomena  of  nature  were  de- 
termined and  controlled  by  some  agent  or  agents  essentially  similar 
to  himself,  but  as  his  knowledge  of  the  world  increased,  the  con- 
trast between  living  and  non-living  things  forced  itself  upon  him 
and  the  idea  of  a  special  vital  principle  of  some  sort  arose.  In  the 
mind  of  different  thinkers  this  principle  has  taken  various  forms, 
and  the  attempt  has  been  made  again  and  again  in  the  history  of 
thought  to  show  that  some  such  principle  is  absolutely  indispen- 
sable for  any  adequate  conception  of  Ufe.  A  century  ago  the  idea 
of  vital  force  dominated  biological  thought. 

Within  recent  years  the  same  idea  has  reappeared  in  a  somewhat 
changed  though  not  essentially  different  form.  Particularly  in 
Germany  a  group  of  investigators  has  arisen  who  believe  that  they 
have  found  new  evidence  in  the  facts  of  experimental  biology  for 
the  existence  of  a  vital  principle.  The  chief  exponent  of  these  ideas 
is  Driesch  ('08)  who  has  developed  the  Aristotelian  idea  of  entele- 
chies  in  a  somewhat  modified  form.  The  entelechy  is  something 
which  acts  in  a  purposive  way  and  constructs  the  organism  for  a 
definite  end  and  controls  its  functioning  after  it  is  constructed. 
The  physico-chemical  processes  are  simply  means  to  the  end. 

Since  the  neo-vitalistic  hypotheses  profess  to  find  their  founda- 
tion to  a  greater  or  less  extent  in  the  facts  of  experimental  biological 
investigation,  they  have  a  claim  on  the  attention  of  biologists  which 
purely  speculative  h>T)otheses  do  not  have.  But  a  critical  examina- 
tion of  the  works  of  Driesch  and  other  neo-vitalists  discloses  the 
fact  that  their  hypotheses  actually  rest,  not  upon  facts,  but  upon 
certain  undemonstrated  and  at  present  undcmonstrable  assump- 
tions. Driesch's  so-called  "proofs  of  the  autonomy  of  vital  pro- 
cesses" are  not  proofs  at  all,  because  each  of  them  involves  in  one 
way  or  another  the  assumption  of  what  it  is  supposed  to  prove.  At 
present  it  is  as  impossible  to  prove  as  to  disprove  the  existence  of  a 

9 


lo  SENESCENCE  AND  REJUVENESCENCE 

vital  principle,  because  our  knowledge  of  the  organism  is  insufficient. 
Only  when  we  have  exhausted  physico-chemical  possibiHties  and 
found  them  to  be  inadequate  shall  we  be  justified  in  searching  else- 
where for  the  basis  of  life. 

But  there  is  one  point  of  particular  interest  in  connection  with 
the  neo-vitahstic  hypotheses.     They  are  a  logical  consequence  of 
the  corpuscular  theories  of  heredity  and  organic  constitution  and 
development,  such  as  the  theory  of  Weismann.     These  theories 
were  widely  current  at  the  time  when  the  neo-vitalistic  school 
arose.     They  themselves  are  fundamentally  ''vi  talis  tic"  in  char- 
acter, whatever  their  assertions  to  the  contrary.     An  orderly  pro- 
gressive development  of  a  definite  character  is  inconceivable  in  an 
organism  composed  of  a  very  large  number  of  independent  ultimate 
units  each  capable  of  growth  and  reproduction,  except  under  the 
influence  of  some  controlhng  and  directing  principle  distinct  from 
the  ultimate  units  themselves.     If  such  theories  represent  the  last 
word  of  science  concerning  the  physico-chemical  constitution  of 
the  organism,  then  we  must  all  be  vitalists,  whether  we  admit  it 
or  not.     But  if  the  controlling  and  determining  principle,  entelechy 
or  whatever  we  choose  to  call  it,  is  indispensable,  why  must  we 
compHcate  matters  by  assuming  the  existence  of  a  multitude  of 
discrete  ultimate  units  of  one  kind  or  another  ?     Why  not  give  the 
entelechy  a  task  worthy  of  it  and  assume  that  all  parts  of  the  organ- 
ism are  essentially  alike  and  equipotential  ?     This  is  practically 
what   Driesch   has  done.     The  entelechy  determines  localization 
and  development  and  uses  physico-chemical  processes  to  effect  its 

ends. 

The  trend  of  biological  thought  has  undergone  change  during 
the  past  twenty  years.  The  development  of  experimental  methods 
on  the  one  hand  and  the  development  of  the  physical  sciences  on 
the  other  have  contributed  to  alter  our  conception  of  the  organism 
and  today  there  is  less  basis  for  vitalistic  theory  than  ever  before. 
Even  the  theory  of  Weismann  and  other  morphological  theories  of 
the  organism  are  giving  place  to  theories  of  a  different  type,  and 
while  many  other  attempts  will  undoubtedly  be  made  in  future  to 
demonstrate  the  indispensabiUty  of  some  sort  of  vital  principle, 
the  analysis  and  synthesis  of  science,  proceeding  step  by  step,  test- 


VARIOUS  THEORIES  OF  THE  ORGANISM  ii 

ing  and  retesting  the  supposed  facts,  adopting  and  discarding  hy- 
potheses, will  continue  to  be  the  basis  of  our  advance  in  knowledge. 

CORPUSCULAR  THEORIES 

During  the  latter  half  of  the  nineteenth  century,  biology,  and 
particularly  zoology,  was  to  a  large  extent  dominated  by  the  cor- 
puscular theories  of  heredity  and  organic  constitution.  These 
theories  postulate  some  sort  of  a  material  particle  or  corpuscle 
consisting  of  more  than  one  molecule  as  the  ultimate  basis  of  life. 
The  organism  is  built  up  in  one  way  or  another  from  a  number, 
often  very  large,  of  such  corpuscles,  and  the  corpuscles  are  the 
"bearers  of  heredity."  The  gemmules  of  Darwin,  the  pangenes 
of  DeVries,  the  physiological  units  of  Spencer,  the  biophores  and 
determinants  of  Weismann,  and  various  other  hypothetical  units 
have  played  an  important  part  in  biological  thought  during  almost 
half  a  century. 

This  group  of  theories  may  be  called  the  morphological  or 
static  group.  They  all  postulate  a  complex  morphological  struc- 
ture as  the  basis  of  inheritance  and  development,  and  they  are  all 
attempts  to  answer  the  question  as  to  how  the  characteristics  of 
the  species  are  maintained  from  one  generation  to  another.  Among 
them  the  theory  of  Weismann  has  been  more  completely  developed 
and  has  influenced  biological  thought  and  investigation  to  a  greater 
extent  than  any  other. 

All  of  these  theories  possess  certain  characteristic  features  in 
common.  The  ultimate  elements,  whatever  they  may  be  called, 
are  not  alike,  but  each  possesses  certain  definite  characteristics  and 
plays  a  definite  part  in  the  development  of  the  individual.  The 
organism  is  in  short  essentially  a  colony  of  such  units.  According 
to  Weismann,  DeVries,  and  others,  the  ultimate  units  are  each 
capable  of  growth,  and  each  reproduces  its  own  kind. 

It  is  scarcely  necessary  to  call  attention  to  the  fact  that  these 
theories  do  not  help  us  in  any  way  to  solve  any  of  the  fundamental 
problems  of  biology;  they  merely  serve  to  place  these  problems 
beyond  the  reach  of  scientific  investigation.  The  hj^Dothetical 
units  are  themselves  organisms  with  all  the  essential  characteristics 
of  the  organisms  that  we  know;  they  possess  a  definite  constitution, 


12  SENESCENCE  AND  REJUVENESCENCE 

they  grow  at  the  expense  of  nutritive  material,  they  reproduce 
their  kind.  In  other  words,  the  problems  of  development,  growth, 
reproduction,  and  inheritance  exist  for  each  of  them  and  the  assump- 
tion of  their  existence  brings  us  not  a  step  nearer  the  solution  of 
any  of  these  problems.  These  theories  are  nothing  more  nor  less 
than  translations  of  the  phenomena  of  life  as  we  know  them  into 
terms  of  the  activity  of  multitudes  of  invisible  hypothetical  or- 
ganisms, and  therefore  contribute  nothing  in  the  way  of  real  ad- 
vance. No  valid  evidence  for  the  existence  of  these  units  exists, 
but  if  their  existence  were  to  be  demonstrated  we  might  well 
despair  of  gaining  any  actual  knowledge  of  life. 

But  these  theories  possess  another  fundamental  defect  in  that 
they  do  not  provide  any  adequate  mechanism  for  the  control 
and  co-ordination  or  dominance  and  subordination  of  the  activity 
of  the  ultimate  units.  It  is  absolutely  inconceivable  that  a  mul- 
titude of  these  units,  such  as  is  assumed  to  constitute  the  basis 
of  the  cell  or  the  organism,  should  always  in  a  given  species 
arrange  themselves  in  a  perfectly  definite  manner  so  as  to  pro- 
duce always  essentially  the  same  total  result.  In  other  words, 
these  theories  do  not  account  satisfactorily  for  the  peculiarly  con- 
stant course  and  character  of  development  and  morphogenesis. 
If  we  follow  them  to  their  logical  conclusion,  which  their  authors 
have  not  done,  we  find  ourselves  forced  to  assume  the  existence  of 
some  sort  of  controlling  and  co-ordinating  principle  outside  the 
units  themselves,  and  superior  to  them.  If  the  units  constitute  the 
physico-chemical  basis  of  life,  as  their  authors  maintain,  then  this 
controlling  principle,  since  it  is  an  essential  feature  of  life,  must  of 
necessity  be  something  which  is  not  physico-chemical  in  nature. 
In  short,  these  theories  lead  us  in  the  final  analysis  to  the  same 
conclusion  as  that  reached  by  the  neo-vitalists.  If  we  are  not 
content  to  accept  this  conclusion  we  must  reject  the  theories. 

The  development  within  recent  years  of  the  experimental 
method  of  investigation  and  the  consequent  approach  of  mor- 
phology and  physiology  toward  a  common  ground  have  accom- 
plished much  in  inducing  biologists  to  turn  their  attention  in  other 
directions  for  interpretation  and  synthesis  of  the  facts.  But  the 
Weismannian  germ  plasm  as  an  entity  distinct  from  the  soma  and 


VARIOUS  THEORIES  OF  THE  ORGANISM  13 

governed  by  different  laws  still  plays  no  small  part  in  interpretation 
and  speculation,  and  we  have  heard  much  of  unit  characters  within 
the  last  few  years.  The  chromosomes  and  their  hypothetical 
constituent  elements  still  serve  their  purpose  as  safe  repositories 
of  unsolved  problems,  and  doubtless  will  long  continue  to  do  so. 
And  in  Rignano's  theory  of  centro-epigenesis  ('06)  we  have  a  cor- 
puscular theory  in  a  new  dress,  but  still  with  the  same  characteristic 
features. 

But  all  of  these  theories  and  conceptions  bear  the  stamp  of  the 
study  rather  than  of  the  laboratory.  Many  of  them  show  great 
ingenuity,  but  they  all  fail  to  show  us  how  the  things  are  done  that 
they  assume  to  be  done:  they  ignore  almost  entirely  the  dynamic 
side  of  Hfe.  At  present  we  can  neither  prove  nor  disprove  them, 
for  they  are  entirely  beyond  the  reach  of  science.  No  facts  can 
overthrow  them,  for  it  is  always  possible  to  make  the  h>'pothetical 
units  behave  as  the  facts  demand.  But  we  can  at  least  look  in 
other  directions  for  a  more  satisfactory  basis  for  interpretation  of 
the  facts  of  observation  and  experiment  and  for  guidance  in  our 
thinking. 

CHEMICAL  THEORY 

The  synthesis  in  the  laboratory  of  organic  substances  which 
began  in  1828  with  the  synthesis  of  urea  by  Wohler  led  to  the 
overthrow  of  the  doctrine  of  vital  force  current  before  that  time. 
The  formulation  of  the  law  of  conservation  of  energy  by  Robert 
Mayer,  its  establishment  by  Helmholtz,  and  its  appHcation  to 
organisms  by  both  of  these  investigators  as  well  as  by  others,  con- 
tributed still  further  to  the  belief  that  the  dynamic  processes  in 
organisms,  instead  of  being  unique  and  governed  by  special  laws, 
are  not  fundamentally  diflferent  from  those  which  occur  inde- 
pendently of  Ufe.  And,  finally,  the  acceptance  of  the  theory  of 
evolution  gave  a  breadth  of  outlook  never  before  attained,  in  that 
it  permitted  us  not  only  to  regard  the  organic  world  as  one  great 
whole,  but  also  afforded  a  firm  foundation  for  the  belief  that  the 
living  must  have  arisen  from  the  lifeless  and  that  the  fundamental 
laws  governing  both  are  the  same. 

With  the  attainment  of  this  point  of  view  the  problem  of  the 
nature  of  the  processes  in  the  living  organism  was  fully  established 


14  SENESCENCE  AND  REJUVENESCENCE 

as  a  scientific  problem.  And  since  it  was  evident  that  chemical 
reactions  play  a  very  large  part  in  hfe  processes  it  became  essen- 
tially a  chemical  problem.  From  this  time  on  our  knowledge  of 
the  chemistry  of  organisms  increased  rapidly,  and  certain  investi- 
gators have  been  so  sanguine  as  to  believe  that  we  were  on  the 
threshold  of  the  synthesis  in  the  laboratory  of  living  matter.  Dur- 
ing the  same  period  the  visible  structural  basis  of  life  was  being 
studied  under  the  microscope.  In  1837-39  the  cell  theory  was 
formulated  by  Schleiden  and  Schwann,  and  in  the  half-century 
following  the  problems  of  cellular  and  protoplasmic  structure 
claimed  the  attention  of  biologists  to  a  large  extent. 

These  investigations  soon  made  it  evident  that  life  is  closely 
associated  in  some  way  with  the  substances  which  we  call  proteids. 
These  are  found  in  all  organisms  and  so  far  as  we  know  nowhere 
else.  Excepting  water,  they  are  the  chief  constituent  of  the  visible 
substance  characteristic  of  organisms,  i.e.,  protoplasm.  It  was  also 
demonstrated  that  life  is  associated  with  a  complex  of  chemical 
activities.  Certain  substances  are  taken  up  by  the  organism  and 
others  are  eliminated.  Between  ingestion  and  elimination  a  com- 
plex series  of  chemical  reactions  was  found  to  occur,  and  the  whole 
process  was  called  metabolism. 

The  conception  of  the  metabolic  process  and  its  relation  to 
protoplasm,  which  was  most  widely  accepted  during  this  period  of 
chemical  and  morphological  investigation  in  the  latter  half  of  the 
nineteenth  century,  was  that  metabolism  consisted  fundamentally 
of  two  parts.  Of  these  one,  the  anabolic  or  assimilative  process, 
was  in  its  essential  features  the  recombination  and  synthesis  of  the 
nutritive  substances  into  extremely  complex  proteid  molecules 
which  constituted  the  "living  substance."  These  proteid  mole- 
cules were  regarded  as  highly  labile  chemically,  or  "explosive,"  so 
that  they  were  able  to  respond  to  stimulation  of  various  kinds  by 
decomposition  and  the  very  rapid  liberation  of  energy.  The  various 
steps  in  the  decomposition  of  these  living  proteid  molecules  consti- 
tuted the  process  of  katabolism  or  dissimilation.  Investigation 
showed  that  the  molecular  weight  of  the  proteids  was  in  general 
very  high,  and  this  was  believed  to  indicate  very  great  complexity 
of  the  molecules.     The  highly  unstable  or  labile  character  of  the 


VARIOUS  THEORIES  OF  THE  ORGANISM  15 

living  proteid  was  believed  to  be  connected  with  its  great  com- 
plexity. Of  course  many  differences  of  opinion  existed  with  respect 
to  the  details  of  the  process,  but  the  essential  feature  of  this  con- 
ception of  the  organism  is  that  Ufe  consists  in  the  building  up  and 
the  breaking  down  of  proteid  molecules.  The  energy  developed 
by  living  forms  is  the  energy  contained  in  these  molecules. 

The  necessity  for  the  distinction  between  living  and  dead  proteid 
was  pointed  out  by  Pfluger  ('75),  and  in  later  years  Verworn  ('03) 
has  developed  the  idea  further  in  his  "  biogene  hypothesis,"  of  which 
the  essential  feature  is  that  certain  complex  labile  proteid  mole- 
cules are  the  biogenes,  the  "producers  of  Ufe."  These  molecules 
are  not  necessarily  entirely  decomposed  in  metabolism,  but  the 
source  of  energy  probably  lies  in  certain  chemical  groups  which 
break  down  and  are  replaced  by  synthesis  from  the  nutritive  sub- 
stances. According  to  this  hypothesis  the  dynamic  processes  in 
the  organism  are  connected  with  the  breakdown  and  synthesis  of 
these  labile  molecules.  The  molecule  is  not  itself  "ahve,"  but  its 
constitution  is  the  basis  of  life  and  life  results  from  the  chemical 
transformations  which  its  lability  makes  possible.  The  "living 
substance"  is  then  not  a  substance  of  uniform  definite  molecular 
constitution:  such  a  substance  would  not  be  alive.  It  is  rather  a 
substance  in  which  some  of  the  labile  molecules  are  continually 
undergoing  transformation,  i.e.,  life  itself  consists  in  chemical 
change,  not  in  chemical  constitution. 

This  theory  of  the  organism  leaves  us  very  much  in  the  dark  on 
many  points.  In  the  first  place,  most  of  the  proteids  as  we  know 
them  in  the  laboratory  are  relatively  stable  and  inert  chemically 
and  show  no  traces  of  the  extreme  lability  or  explosiveness  which 
the  theory  postulates  as  their  most  important  characteristic  in  the 
living  organism.  This  difficulty  was  solved  theoretically  by  assum- 
ing that  the  lability  is  a  property  of  living  proteids  only  and  dis- 
appears with  death.  Death  in  fact  was  regarded  as  resulting  from 
this  change  from  lability  to  stability.  The  proteids  in  vitro  are 
of  course  dead  proteids,  therefore  we  should  not  expect  to  find  them 
possessing  the  property  of  labihty.  This  assumed  distinction  be- 
tween living  and  dead  substance  has  the  further  disadvantage  of 
practically   removing   the   "Hving  substance"   from  the   field   of 


1 6  SENESCENCE  AND  REJUVENESCENCE 

investigation,  for  as  soon  as  we  attempt  to  determine  how  it  differs 
from  dead  substance  death  occurs. 

Moreover,  if  death  results  from  change  from  extreme  labihty 
to  relatively  high  stability  we  should  expect  at  least  many  of  the 
proteids  of  the  body  to  undergo  marked  changes  in  appearance  and 
physical  properties  at  the  time  of  death.  Some  changes  of  this 
sort,  such  as  coagulation,  do  occur,  but  coagulation  does  not  neces- 
sarily involve  chemical  transformation,  and  in  general  the  visible 
changes  in  the  proteids  with  death  are  not  very  great.  Certainly 
they  are  not  as  great  as  would  be  expected  if  such  a  profound 
chemical  change  occurs. 

If  the  energy  of  the  organism  is  due  to  the  explosive  trans- 
formation of  highly  labile  molecules  into  more  stable  conditions 
and  if  death  also  results  from  a  more  extreme  change  of  the  same 
sort  in  the  substance  of  the  organism,  we  should  expect  to  find  a 
very  large  amount  of  energy  developed  at  the  time  of  death.  If 
all  the  living  substance  changes  into  dead  substance  in  the  course 
of  a  few  moments  or  a  few  hours,  or  even  a  few  days,  what  becomes 
of  the  energy  liberated  ?  The  amount  of  energy  developed  by  such 
a  change  would  necessarily  be  greater  than  that  resulting  from  the 
most  extreme  stimulation  which  did  not  kill,  for  such  stimulations 
are  supposed  always  to  leave  some  part  of  the  hypothetical  living 
substance  intact.  Such  a  liberation  of  energy  could  scarcely  fail 
to  produce  profound  changes  of  some  sort,  either  mechanical, 
electrical,  or  thermic,  but  death  is  not  necessarily  accompanied  by 
any  energetic  changes  of  such  magnitude  as  might  be  expected  to 
occur  according  to  the  hypothesis. 

How,  we  must  also  ask,  are  we  to  account  for  growth  on  this 
basis  ?  What  peculiar  property  of  the  living  substance  determines 
not  only  that  the  molecules  which  break  down  shall  again  be  built 
up  or  replaced,  but  that  other  new  molecules  shall  be  added? 
Various  highly  hypothetical  answers  have  been  given  to  this  ques- 
tion, but  the  fact  remains  that  so  far  as  we  know  no  similar  process 
exists  elsewhere  in  the  world.  The  growth  of  crystals  has  often 
been  compared  with  that  of  organisms,  but  the  resemblance  is  at 
best  only  very  remote,  for  growth  in  the  organism  is  certainly  closely 
associated  with  chemical  reaction  of  a  complex  character,  while  in 
the  crystal  it  results  from  a  physical  relation  between  like  molecules. 


VARIOUS  THEORIES  OF  THE  ORGANISM  17 

The  solution  of  the  problem  of  differentiation  has  scarcely  been 
attempted.  It  is  manifestly  closely  associated  with  the  metabohc 
process,  but  what  is  the  origin  and  significance  of  the  different 
kinds  of  proteid  substance  and  how  is  their  localization  at  different 
points  of  the  organism  accomplished?  If  the  ''labile"  biogene 
molecules  all  possess  the  same  constitution,  then  they  must  undergo 
different  transformations  in  different  parts  of  the  organism;  if 
they  differ  in  constitution  in  different  parts  we  must  find  some 
basis  for  the  difference.  It  is  an  established  fact  that  the  basis  of 
differentiation  exists  within  the  organism  and  not  in  environmental 
factors:  it  must  then  depend  in  some  way  upon  the  labile  proteid 
molecule  which  according  to  the  hypothesis  is  the  basis  of  hfe. 
But  it  is  difficult  to  understand  how  such  molecules  can  serve  as  a 
foundation  for  localization  and  differentiation. 

If  we  accept  this  hypothesis  we  must  after  all  conclude  that  the 
processes  in  the  living  organism  dift'er  very  widely  from  those  in 
the  inorganic  world,  for  nowhere  except  where  there  is  life  do  we 
find  anything  approaching  in  any  degree  the  synthesis  of  so  com- 
plex and  highly  labile  a  substance  as  the  Hving  substance  is  assumed 
to  be.  But  even  if  we  should  ever  succeed  in  producing  in  the 
laboratory  a  proteid  with  the  degree  of  labihty  postulated  for  the 
living  substance,  it  would  be  likely,  in  the  absence  of  the  delicate 
mechanism  regulating  its  transformation  in  the  organism,  to  die 
or  "explode"  at  once. 

From  this  point  of  view  it  is  also  difficult  to  account  for  the 
capacity  of  organisms  to  continue  alive  when  subjected  to  the 
never-ceasing  changes  in  the  world  about  them.  We  should 
scarcely  expect  such  extremely  delicate  and  sensitive  mechanisms 
as  these  highly  labile  molecules  to  withstand  the  shocks  to  which 
organisms  in  nature  are  constantly  subjected.  The  facts  indicate 
that  organisms  have  existed  continuously  for  millions  of  years  and 
during  this  time  have  given  rise  to  inconceivable  amounts  of 
"living  substance."  How  could  such  a  labile  substance  ever  have 
persisted  long  enough  in  the  first  instance  to  form  an  organism  ? 

The  only  way  in  which  we  can  account  for  these  facts  without 
discarding  the  hypothesis  of  a  highly  labile  living  substance  is  by 
the  assumption  that  in  some  way  a  part  of  the  energy  liberated  by 
the  breakdown  of  these  labile  molecules  must  serve  for  the  synthesis 


i8  SENESCENCE  AND  REJUVENESCENCE 

of  new  molecules  from  the  nutritive  substances.  In  other  words, 
the  living  substance  once  produced  is  self-perpetuating,  at  least 
within  a  very  wide  range  of  external  conditions.  But  if  the  abihty 
to  perpetuate  itself  in  this  way  is  a  property  of  the  living  substance, 
then  it  is  in  this  respect  also  very  different  from  any  other  sub- 
stance with  which  we  are  acquainted. 

It  appears  then  that  when  we  analyze  this  hypothesis  of  a  labile 
proteid  substance  which  gives  rise  to  the  manifestations  of  life  by 
its  chemical  transformations  we  find  that  it  does  not  help  us  to 
any  great  extent  in  bridging  the  gap  between  the  organism  and  the 
inorganic  world.  The  self-perpetuating  substance  or  substances 
which  constitute  the  basis  of  life  remain  unique  in  character. 
They  are  highly  labile,  yet  persist  under  a  great  variety  of  con- 
ditions, and  ''die"  in  most  cases  without  the  liberation  of  any  very 
great  amount  of  energy.  During  life  they  regulate  their  own 
chemical  changes  in  some  way,  they  determine  the  formation  of 
new  molecules  like  themselves,  and  they  are  responsible  somehow 
for  an  orderly  sequence  of  differentiation  of  parts  of  the  organism. 
Evidently  they  are  very  different  from  other  chemical  substances, 
even  highly  labile  ones,  with  which  we  are  familiar. 

The  numerous  difficulties  which  arise  in  connection  with  hy- 
potheses of  this  character  must  at  least  raise  the  question  whether 
the  point  of  view  on  which  they  are  based  is  fundamentally  correct. 
Is  life  at  bottom  simply  a  complex  of  chemical  reactions  or  is  there 
some  other  factor  involved  which  the  hypothesis  of  a  labile  mole- 
cule as  the  basis  of  life  fails  to  take  into  account  ?  In  the  following 
sections  an  attempt  is  made  to  answer  this  question. 

PHYSICO-CHEMICAL  THEORY 

A  few  years  ago  the  existence  of  a  living  substance  as  a  more  or 
less  definite  chemical  compound  was  very  generally  accepted,  and 
only  rarely  were  criticisms  and  questionings  heard.^ 

'  See  for  example  A.  P.  Mathews,  '99,  '05;  Driesch,  '01  (pp.  140-52).  Mathews 
pointed  out  that  living  matter  must  be  a  mixture  of  many  substances  among  which 
various  chemical  reactions  occur.  Driesch  denies  very  posirively  the  existence  of  a 
definite  Hving  substance,  but  for  him  this  is  merely  one  point  in  the  argument  for  the 
autonomy  of  vital  processes. 


VARIOUS  THEORIES  OF  THE  ORGANISM  19 

In  his  book  on  the  physical  chemistry  of  the  cell  and  tissues, 
Hober  ('11,  pp.  553-55)  asserts  that  we  have  absolutely  no  grounds 
for  beheving  that  the  metabolic  process  is  based  on  the  lability  of  a 
complex  organic  component  of  the  protoplasm.  When  we  attempt 
to  solve  the  problems  of  metabolism  with  the  aid  of  this  hypothetical 
labile  molecule,  we  find  ourselves  in  a  cul  de  sac  from  which  the 
only  possible  way  out  is  retreat.  According  to  Hober,  and  most 
authorities  now  agree  with  him,  there  is  no  kind  of  proteid  essen- 
tially different  from  that  with  which  we  are  familiar  in  the  labora- 
tory. If  proteids  are  readily  broken  up  in  the  organism,  it  is  not 
because  in  some  way  they  have  acquired  a  peculiar  property  of 
lability  which  they  do  not  possess  elsewhere,  but  for  very  different 
reasons;  the  conditions  in  the  organism  are  different  from  those  in 
the  test-tube.  Hober  maintains  that  the  fundamental  charac- 
teristic of  the  process  of  metabohsm  is  to  be  found  in  the  combined 
and  correlated  activity  of  certain  definite  substances  in  certain 
definite  quantitative  relations. 

This  conception  of  metabohsm  has  gained  ground  rapidly  of 
late  and  for  various  reasons.  In  the  first  place,  evidence  in  its 
favor  has  been  rapidly  accumulating,  and  there  is  not  a  shred  of 
experimental  evidence  in  support  of  the  labile  molecule  hypothesis. 
It  is  all  the  time  becoming  more  evident  that  life  does  not  consist 
in  any  one  process  nor  depend  on  a  particular  kind  of  molecule, 
but  that  it  is  the  result  of  many  processes  occurring  under  con- 
ditions of  a  certain  kind  and  influencing  each  other.  Moreover, 
such  a  conception  has  a  logical  advantage  over  the  hypothesis  of 
the  labile  molecule  in  that  it  does  not  involve  assumptions  which 
are  outside  the  range  of  scientific  investigation  and  which  we  can 
therefore  never  hope  to  prove  or  disprove. 

If  we  accept  this  idea  we  must  abandon  the  assumption  of  a 
living  substance  in  the  sense  of  a  definite  chemical  compound. 
Life  is  a  complex  of  dynamic  processes  occurring  in  a  certain  field 
or  substratum.  Protoplasm,  instead  of  being  a  peculiar  living  sub- 
stance with  a  peculiar  complex  morphological  structure  necessary 
for  life,  is  on  the  one  hand  a  colloid  product  of  the  chemical  reac- 
tions, and  on  the  other  a  substratum  in  which  the  reactions  occur 
and  which  influences  their  course  and  character  both  physically  and 


20  SENESCENCE  AND  REJUVENESCENCE 

chemically.     In  short,  the  organism  is  a  physico-chemical  system 
of  a  certain  kind. 

One  point  should  perhaps  be  emphasized.  The  importance  of 
the  proteids  for  life  is  no  less  according  to  this  theory  than  on  the 
assumption  of  the  labile  proteid  molecule.  But  the  proteids  are 
physical  as  well  as  purely  chemical  factors  in  the  result.  We  know 
also  that  metabolism  is  not  simply  a  process  of  building  up  and 
breaking  down  of  proteids,  and  that  the  proteids  of  the  protoplasm 
are  only  one  of  the  products  of  the  reaction-complex  and  may  or 
may  not  play  an  important  chemical  role  after  their  formation. 
Since  the  investigations  of  recent  years  point  more  and  more  clearly 
to  some  such  physico-chemical  conception  of  the  organism  as 
this  as  the  only  satisfactory  working  hypothesis,  it  is  necessary 
to  consider  certain  features  of  the  organism  in  the  light  of 
this  conception. 

THE  COLLOID  SUBSTRATUM  OF  THE  ORGANISM 

The  classical  investigations  of  Kossel  and  Emil  Fischer  have 
estabHshed  a  firm  foundation  for  the  belief  that  the  complexity  of 
the  proteid  molecule  is  not  as  great  as  was  formerly  believed.  The 
proteids  are  apparently  built  up  from  certain  relatively  simple 
chemical  compounds,  the  amino-acids  and  their  derivatives,  to- 
gether with  certain  other  substances,  and  the  proteid  molecule, 
though  very  large,  apparently  consists  essentially  of  a  number  of 
these  components  linked  together.  Of  course  such  a  constitution 
affords  the  possibility  of  a  very  great  variety  of  chemical  reactions, 
but  it  does  not  afford  a  basis  for  the  assumption  of  extreme  labiHty 
in  the  proteids  of  the  living  organism.  On  the  contrary  the  results 
of  chemical  as  well  as  of  morphological  investigation  indicate  that 
at  least  many  of  the  proteids  are  relatively  stable  in  the  living 
organism  as  well  as  in  the  test-tube. 

The  proteids  exist  in  the  colloid  condition.  Graham  ('6i) 
distinguished  two  groups  of  substances,  the  colloids  and  crystal- 
loids, and  although  we  now  know  that  no  sharp  distinction  exists 
between  the  two  groups  and  that  any  substance  may,  at  least 
theoretically,  exist  in  the  colloid  condition,  certain  substances 
usually  appear  as  colloids  and  others  as  crystalloids.     In  general 


VARIOUS  THEORIES  OF  THE  ORGANISM  2i 

the  more  complex  the  constitution  of  a  substance  the  more  likely 
it  is  to  exist  in  the  colloid  condition. 

The  colloids  are  disperse  heterogeneous  systems,  i.e.,  they 
consist  essentially  of  particles  larger  than  molecules  of  a  substance 
or  substances  in  a  medium  of  dispersion  which  may  be  water  or 
some  other  fluid.  In  the  colloid  solution,  or  "sol,"  the  particles 
are  suspended  and  separated  from  each  other  by  the  medium, 
while  in  the  coagulated  condition,  or  "gel,"  they  are  more  or  less 
aggregated.  As  regards  the  size  of  the  particles,  the  colloid  may 
range  from  a  suspension  or  emulsion  in  which  the  particles  are 
visible  to  the  naked  eye  to  the  molecular  true  solution  at  the  oppo- 
site extreme.  The  colloids  are  usually  divided  into  two  groups, 
the  suspensoids,  in  which  the  particles  are  solid,  and  the  emul- 
soids,  in  which  they  are  fluid  or,  more  properly,  contain  a  high  per- 
centage of  fluid. 

The  suspensoids  are  comparatively  unstable  as  regards  the 
colloid  condition,  are  readily  precipitated  or  coagulated  by  salts, 
carry  a  constant  electric  charge  of  definite  sign,  are  not  viscous, 
usually  do  not  swell,  do  not  show  a  lower  surface  tension  than  the 
pure  medium  of  dispersion,  and  are  mostly  only  slightly  reversible. 

The  emulsoids,  however,  are  comparatively  stable  as  colloids, 
less  readily  coagulated  by  salts,  may  become  either  positively  or 
negatively  charged,  are  usually  viscous  and  possess  a  lower  surface 
tension  than  the  medium  of  dispersion,  form  membranes  at  their 
limiting  surfaces,  and  are  reversible  to  a  high  degree.' 

Most  of  the  organic  colloids  together  with  some  other  sub- 
stances belong  to  the  second  group,  the  emulsoids,  and  it  is  demon- 
strated beyond  a  doubt  that  many  of  the  characteristic  features  of 
living  organisms  are  due  to  the  presence  of  a  substratum  composed 
of  these  colloids.  The  viscosity,  the  reversible  changes  in  aggre- 
gate condition  through  all  gradations  from  sol  to  gel  and  back 
again,  the  ability  to  take  up  water  and  swell,  and  the  formation  of 
membranes  as  well  as  the  other  properties  are  of  great  significance 

'  Books  on  colloids  are  rapidly  becoming  numerous.  See  for  example  Freund- 
lich,  '09,  and  Wolfgang  Ostwald,  '12,  as  general  works  on  the  subject.  Bcchhold, 
'12,  Hober,  '11,  and  Zanger,  '08,  consider  the  significance  of  the  colloids  for  the  living 
organism. 


22  SENESCENCE  AND  REJUVENESCENCE 

for  the  phenomena  of  Hfe.  The  organic  colloids  are  chiefly  proteid 
or  fatty  in  nature,  and  the  present  state  of  our  knowledge  indicates 
that  the  properties  of  these  substances  as  colloids  are  no  less  im- 
portant for  the  living  organism  than  their  chemical  constitution. 

In  every  living  organism  known  to  us  the  chemical  processes 
of  metaboHsm  take  place  in  a  complex  colloid  field  or  substratum, 
and  many  of  the  pecuharities  of  the  metabolic  processes  are  unques- 
tionably due  to  this  fact.  Within  recent  years  the  significance  of 
colloids  for  the  phenomena  of  life  has  been  pointed  out  again  and 
again.  Bechhold  in  his  recent  book  ('12)  goes  so  far  as  to  assert 
that  Ufe  is  inconceivable  except  in  a  colloid  system.  Doubtless 
"  colloid  chemistry"  is  at  present  the  fashion,  but  it  is  also  true  that 
this  fashion  has  a  certain  justification.  The  study  of  the  behavior 
and  properties  of  colloids  has  thrown  new  light,  not  only  on  many 
problems  of  chemistry  and  physics,  but  on  many  problems  of  biology 
as  well.  Attention  may  briefly  be  called  to  a  few  of  these  biological 
problems. 

The  problems  of  localization  and  morphogenesis  assimie  a  new 
form  in  the  light  of  our  knowledge  of  colloids.  In  the  course  of 
development  of  the  organism  certain  processes  become  localized 
at  certain  points  and  morphological  structure  and  differentiation 
result.  The  visible  basis  of  morphogenesis  is  the  protoplasm,  and 
in  it  the  structural  features  arise.  The  definiteness  and  persistence 
of  organic  structure  in  a  substance  like  protoplasm  which  presents 
all  conditions  between  a  concentrated  and  a  very  dilute  gel  or  a  sol 
has  always  presented  many  difficulties,  and  the  problem  is  at 
present  by  no  means  solved.  The  attempt  has  been  made  repeat- 
edly to  find  in  the  process  of  crystallization  and  the  definiteness  of 
form  in  the  crystal  a  basis  for  organic  form  and  structure,  but  with- 
out any  very  satisfactory  results.  The  resemblance  between  the 
physical  process  of  crystalhzation  in  a  substance  of  uniform  consti- 
tution and  the  development  of  form  and  structure  in  connection 
with  chemical  reaction  in  the  complex  organism  is  certainly  not 
very  close. 

Under  proper  conditions  it  is  possible  to  produce  more  or  less 
definite  forms  by  means  of  chemical  reaction,  but  in  all  such  cases 
we  find  that  the  form  is  not  directly  dependent  upon  the  reaction 


VARIOUS  THEORIES  OF  THE  ORGANISM 


23 


but  upon  particular  osmotic  or  other  physical  conditions  which  are 
present  in  the  experiment.  Structures  so  produced  are  often 
evanescent  and  disappear  as  the  conditions  in  the  medium  change, 
for  the  chemical  processes  do  not  remain  localized  in  the  ordinary- 
media  of  chemical  reaction,  though  where  the  substance  of  the 
structure  is  insoluble  they  may  persist. 

Within  recent  years  it  has  been  shown  that  the  production  of 
form  and  structure  in  connection  with  chemical  reaction  is  much 
more  readily  accomplished  when  the  reaction  occurs  in  the  presence 
of  colloids.  The  colloids  in  such  cases  are  not  necessarily  involved 
in  the  chemical  reaction  in  any  way,  but  act  primarily  as  a  physical 
substratum  in  which  the  reaction  occurs.  By  altering  the  course 
and  rate  of  diffusion  they  serve  to  establish  or  maintain  differences 
of  concentration;  in  consequence  of  the  great  amount  of  surface  of 
the  colloid  particles  adsorption  may  play  an  important  part,  and 
the  formation  of  membranes  may  also  affect  the  course  of  the  re- 
action. The  effect  of  the  colloid  as  a  localizing  factor,  as  a  means 
of  producing  form  and  structure,  is  greater  in  the  gel  than  in  the 
sol  state  of  aggregation.^ 

Many  have  not  been  slow  to  call  attention  to  the  resemblance 
between  form  and  structure  thus  produced  and  organic  form  and 
structure,  and  more  or  less  adventurous  hypotheses  of  the  nature 
of  life  have  been  one  result  of  such  researches.  On  the  other  hand, 
many  biologists  have  been  inclined  to  regard  experimentation  of 
this  sort  as  of  little  value  for  the  problem  of  morphogenesis,  but 
this  attitude  seems  to  arise  in  part  from  a  misconception.  The  most 
important  point  in  connection  with  such  experiments  is  not  the 
resemblance  between  the  forms  and  structures  produced  and  those 
of  living  organisms.  Actually  of  course  the  resemblances  are  in 
many  cases  very  remote  and  superficial  and  of  minor  importance. 
But  the  fact  that  morphological  form  and  structure  can  be  made 
to  arise  in  such  physico-chemical  systems  is  of  great  importance 
for  biology,  for  it  affords  at  least  a  basis  for  the  scientific  investiga- 
tion and  interpretation  of  morphogenesis  in  the  organism.  Earlier 
attempts  to  formulate  theories  of  morphogenesis  have  consisted  in 

'  Examples  of  investigation  along  this  line  are  the  work  of  Leduc,  '08,  '09a,  'ogb, 
'10;  Liesegang,  '09,  '11,  '14,  and  other  earlier  papers,  and  Kuster,  '13. 


24  SENESCENCE  AND  REJUVENESCENCE 

most  cases  simply  in  the  postulation  of  a  complex  invisible  morpho- 
logical structure  of  one  kind  or  another  as  the  basis  of  the  visible 
structure  which  develops ;  with  such  theories  the  problem  of  struc- 
ture remains  and  is  less  accessible  than  before. 

The  experiments  mentioned  above  demonstrate  that  such  a  com- 
plex invisible  structure  is  quite  unnecessary  as  a  basis  for  visible 
morphogenesis.  In  the  case  of  many  of  the  artificial  structures  the 
determining  conditions  are  not  at  all  complex  and  the  process  is 
readily  analyzed.  It  is  certainly  not  too  much  to  say  that  these 
experiments  in  the  production  of  form  constitute  a  real  and  impor- 
tant step  toward  the  solution  of  the  problem  of  organic  morpho- 
genesis. From  them  we  can  at  least  see  the  possibility  and  even 
the  probability  of  reducing  the  problem  of  structure  to  other  and 
simpler  terms,  that  is  to  say,  terms  of  dynamic  processes,  and  that 
must  be  reckoned  as  no  slight  advance. 

But  the  colloid  substratum  in  the  organism  is  of  importance  in 
many  other  ways.  The  capacity  of  many  of  the  organic  colloids 
for  taking  up  water  is  of  very  great  importance  in  determining  and 
maintaining-  the  water  content  of  organisms.  A  certain  water 
content  is  indispensable  for  the  normal  activity  of  every  organism 
and  every  part.  We  know,  moreover,  that  various  inorganic 
substances  alter  the  capacity  of  colloids  to  take  up  or  hold  water 
and  evidence  is  rapidly  accumulating  that  many  normal  and  patho- 
logical variations  in  water-content  are  at  least  in  part  determined 
by  changes  in  the  colloids  which  in  turn  result  from  changes  in  the 
content  of  certain  inorganic  salts  and  other  substances. 

The  content  and  distribution  of  the  salts  themselves  is  also 
influenced  by  the  colloids.  Changes  in  the  colloids  alter  the  salt- 
content,  as  regards  either  amount  or  kind.  The  permeabiUty  of 
colloid  membranes  to  the  ions  of  salts  and  other  substances  and  the 
changes  which  they  undergo  with  changes  in  conditions  is  beheved 
by  many  to  be  of  great  importance  for  many  of  the  processes  of 
life.  Authorities  are  not  fully  agreed  as  to  the  part  played  by 
colloid  surface  membranes  in  organisms.  While  the  theory  of  semi- 
permeable membranes  and  of  changes  in  permeabihty  has  been 
very  widely  accepted,  there  are  some  facts  which  indicate  that 
other  factors  besides  membranes  are  concerned  in  the  penetration 


VARIOUS  THEORIES  OF  THE  ORGANISM  25 

of  substances,  and  that  differences  in  the  aggregate  condition  of 
different  parts  are  important  factors  in  the  process. 

But  even  if  membranes  play  the  important  part  which  the 
membrane  theory  assigns  to  them,  there  is  no  general  agreement  as 
to  the  nature  of  the  conditions  which  determine  permeability, 
semi-permeabiUty,  and  impermeability.  Some  maintain  that  these 
properties  of  membranes  depend  upon  their  chemical  constitution, 
and  that  most  substances  to  enter  the  cell  must  combine  chemically 
with  the  substance  of  the  membrane.  Others  believe  that  the 
entrance  of  substances  into  the  cell  is  a  matter  of  solubility  in  the 
membrane-substance.  According  to  the  famihar  theory  of  Overton 
and  Meyer,  the  chief  constituents  of  the  cell  membrane  are  lipoids, 
and  the  passage  of  at  least  many  substances  depends  on  their 
solubihty  in  these  lipoids.  There  is,  however,  considerable  evi- 
dence against  this  view  that  lipoids  are  in  all  cases  the  chief  or  only 
factors  concerned.  Still  another  hypothesis  is  that  the  selective 
capacity  of  the  membrane  depends  in  one  way  or  another  upon 
its  colloid  condition.  It  may  well  be  that  many  different  factors 
are  involved  in  the  permeabihty  of  membranes  in  living  organisms, 
but  it  seems  certain  that  whatever  the  nature  of  these  factors  may 
prove  to  be,  the  pecuHarities  of  the  so-called  living  substance  in 
this  respect  are  very  closely  connected  with  its  colloid  condition. 
And  when  we  recall  the  slight  diffusibihty  of  colloids  through  each 
other,  it  becomes  evident  that  the  colloid  condition  of  the  sub- 
stratum is  an  important  factor  in  determining  the  accumulation 
and  localization  of  colloids  themselves. 

It  has  been  shown  that  various  inorganic  colloids,  such  for 
example  as  colloid  platinum,  resemble  to  some  extent  in  their  action 
as  catalyzers  the  enzymes  or  ferments  of  the  organism.  All  the 
known  organic  enzymes  are  apparently  colloids,  and  while  there  is 
still  difference  of  opinion  as  to  the  nature  of  their  action,  yet  the 
resemblance  between  them  and  inorganic  catalyzers  is  at  least 
highly  suggestive.'  We  know  that  enzymes  are  absolutely  essential 
factors  in  the  processes  of  life,  and  if  enzyme  action  is  in  any  way 
associated  with  the  colloid  condition  the  significance  of  this  con- 
dition for  organic  life  will  be  still  further  demonstrated. 

'  See  Bredig,  '01;  Hober,  '11,  pp.  553-614. 


kJit    fl       I    1^1^  A  ^1 


26  SENESCENCE  AND  REJUVENESCENCE 

The  transmission  of  stimuli  in  living  tissues  is  also  very  com- 
monly regarded  as  dependent  in  some  way  upon  the  colloid  con- 
dition, although  here  again  there  are  differences  of  opinion  as  to 
the  exact  nature  of  the  process. 

Our  knowledge  of  the  colloids  and  particularly  of  the  organic 
colloids  is  far  from  complete;  undoubtedly  the  future  will  clear  up 
many  points  which  are  now  obscure,  but  even  now  it  is  clear  that 
the  colloid  substratum  in  which  the  chemical  reactions  of  metab- 
olism occur  is  an  essential  factor  in  making  the  phenomena  of  hfe 
what  they  are.  Bechhold  ('12),  referring  to  the  possibihty  of  Hfe 
on  other  planets,  asserts  that  whatever  the  substances  may  be  which 
make  up  such  organisms  they  must  be  colloids.  In  fact,  the  more 
we  know  concerning  colloids  the  less  possible  it  becomes  to  con- 
ceive of  anything  similar  to  what  we  regard  as  Ufe  apart  from  them. 
Whatever  else  it  may  be,  it  seems  certain  that  the  organism  is  a 
colloid  system.  From  this  point  of  view  our  definition  of  a  living 
organism  must  be  somewhat  as  follows:  A  Uving  organism  is  a 
specific  complex  of  dynamic  changes  occurring  in  a  specific  colloid 
substratum  which  is  itself  a  product  of  such  changes  and  which 
influences  their  course  and  character  and  is  altered  by  them. 

THE  RELATION  BETWEEN  STRUCTURE  AND  FUNCTION 

The  definition  of  the  organism  given  above  leads  us  to  very 
definite  conclusions  concerning  the  relation  between  structure  and 
function. 

The  dynamic  processes  which  occur  in  organisms  do  not  and 
cannot  constitute  hfe  in  the  absence  of  the  colloid  substratum,  nor 
is  the  colloid  substratum  ahve  without  the  dynamic  processes. 
But  since  the  colloids  characteristic  of  the  organism  are  among  the 
products  of  the  dynamic  processes,  it  is  also  evident  that  the  pro- 
cesses cannot  go  on  in  their  entirety  without  producing  the  colloid 
substratum.  In  other  words,  neither  structure  nor  function  is 
conceivable  except  in  relation  to  each  other. 

The  beginning  of  life  is  to  be  sought  neither  in  a  particular 
complex  of  chemical  reactions  nor  in  a  special  morphological  struc- 
ture. Both  the  reactions  and  the  colloid  substratum  are  necessary 
for  life.     But  since  the  substratum  is  formed  in  the  course  of  the 


VARIOUS  THEORIES  OF  THE  ORGANISM  27 

reactions,  it  is  evident  that  the  association  between  the  reaction- 
complex  and  the  substratum  must  continue  as  long  as  the  reaction- 
complex  continues.  It  is  probable  that  if  we  could  duplicate  the 
reaction-complex  in  the  laboratory  it  would  be  impossible  to 
designate  any  particular  point  in  the  process  as  the  point  where 
life  begins.  Life  is  not  any  particular  reaction  nor  any  particular 
substance,  but  a  great  system  of  processes  and  substances.  Struc- 
ture and  function  are  then  indissociable.  And  yet  in  the  broad 
sense  function  produces  structure  and  structure  modifies  function. 
At  first  glance  it  may  appear  that  this  relation  is  quite  unique,  that 
nothing  like  it  exists  in  the  inorganic  world.  As  a  matter  of  fact, 
however,  the  same  relation  exists  everywhere  in  dynamic  systems 
in  nature. 

Various  authors  have  from  time  to  time  compared  the  organism 
with  one  or  another  inorganic  system.  Roux  ('05),  for  example, 
has  carried  out  in  some  detail  the  comparison  between  the  organism 
and  the  flame.  Although  this  analogy  contains  much  that  is  valu- 
able, especially  on  the  chemical  side,  it  is  imperfect  morphologically 
because  the  morphology  of  the  flame  is  much  less  stable  and  per- 
sistent than  that  of  the  organism.  Some  years  ago  (Child,  '11)  I 
found  the  analogy  between  the  organism  and  a  flowing  stream  I 
useful  for  purposes  of  illustration.  While  as  regards  metabolism  j 
the  river  is  much  more  widely  different  from  the  organism  than 
the  flame,  yet  as  regards  the  relation  between  structure  and  func-  ^ 
tion  there  are  certain  resemblances  between  the  two  which  are  of 
value  for  the  present  purpose.  Such  analogies  serve  merely  to 
call  attention  to  certain  points.  The  flow  of  water — the  current 
of  the  stream — -is  the  dynamic  process  and  is  comparable  in  a  \ 
general  way  to  the  current  of  chemical  energy  flowing  through  the 
organism.  On  the  other  hand,  the  banks  and  bed  of  the  stream 
represent  the  morphological  features.  Wherever  such  a  system 
exists,  certain  characteristic  developmental  changes  occur  which, 
though  much  less  definite  and  fixed  in  localization  and  character 
than  in  the  organism,  are  nevertheless  of  such  a  nature  that  we 
can  predict  and  control  them. 

Neither  water  alone  nor  the  banks  and  bed  alone  constitute 
the  system  which  we  call  a  river;  and  in  nature  the  banks  and  bed 


28  SENESCENCE  AND  REJUVENESCENCE 

and  the  current  have  been  associated  from  the  beginning.  Here 
also  structure  and  function  are  connected  as  in  the  organism:  the 
configuration  of  the  channel  modifies  the  intensity  and  course  of 
the  current  and  the  current  in  turn  modifies  the  morphology  of 
the  channel  by  deposition  at  one  point,  giving  rise  to  structures 
such  as  bars,  islands,  flats,  and  by  erosion  at  another.  And  besides 
this,  the  river  possesses  a  considerable  capacity  for  self-regulation. 
Where  the  channel  is  narrower  the  rate  of  flow  is  higher,  and  vice 
versa.  A  dam  raises  the  level  until  equiUbration  results  and  the 
flow  continues.  It  is  of  course  true  that  only  in  the  lower  reaches 
does  the  river  resemble  the  organism  in  the  accumulation  of 
structural  material:  over  most  of  its  course  it  is  primarily  an 
erosive  agency.  It  does,  however,  exhibit  what  we  may  call  a 
physical  metabolism  on  which  its  morphogenesis  depends.  The 
current  carries  certain  materials  and  the  character  of  these  differs 
with  the  current.  When  the  energy  of  the  current  is  no  longer 
able  to  carry  them  they  are  deposited  and  take  part  in  the  building 
up  of  structure.  Certain  materials  are  more  readily  carried  by 
the  stream  than  others,  and  these  may  be  eliminated  from  the  river 
and  take  no  part  in  its  morphogenesis. 

But  the  most  important  point  for  present  purposes  is  that  in 
the  river,  as  in  the  organism,  structure  and  function  are  indis- 
sociable  and  react  upon  each  other.  From  the  moment  the  current 
begins  to  flow  it  is  a  constructing  agent,  i.e.,  it  determines  form 
along  its  channel,  and  from  the  same  moment  the  structure  already 
existing  affects  the  flow  of  the  current.  It  is  evident  then  that  the 
relation  between  structure  and  function  in  the  living  organism  is 
not  fundamentally  different  from  that  in  the  flowing  stream. 
Structure  and  function  are  indissociable  and  mutually  determining 
as  long  as  the  river  exists  and  the  organism  lives.  In  a  very  inter- 
esting series  of  papers  Warburg'  has  recently  demonstrated  the 
close  interrelation  between  function  and  structure  for  the  oxidation 
processes  and  the  fundamental  structure  of  the  cell,  the  occur- 
rence of  the  oxidations  being  very  directly  dependent  upon  the 
existence  of  the  cell  structure. 

'Warburg,  '12a,  '126,  '13,  '14a,  '14b. 


VARIOUS  THEORIES  OF  THE  ORGANISM  29 

The  living  organism  has  often  been  compared  to  a  machine  made 
by  man,  such  as  the  steam  engine,  which  converts  a  part  of  the 
energy  of  the  fuel  into  function  as  the  organism  transforms  the 
energy  of  nutrition  into  functional  activity.  This  analogy  is  a 
very  imperfect  one,  for  in  the  steam  engine  and  in  all  other  machines 
constructed  by  man  structure  and  function  are  separable.  More- 
over, the  man-made  machine  does  not  construct  itself  by  its  func- 
tional activity,  but  is  completely  passive  as  regards  its  construction, 
being  built  up  by  an  agent  external  to  itself  for  a  definite  purpose, 
and  being  unable  to  function  until  its  structure  is  completed.  The 
organism,  on  the  other  hand,  functions  from  the  beginning  and  con- 
structs itself  by  its  own  functional  activity;  and  the  structure 
already  present  at  any  given  time  is  a  factor  in  determining  the 
function,  and  the  function  at  any  given  time  is  a  factor  in  determin- 
ing the  future  structure.  The  organism  is  then  a  very  different 
thing  from  a  man-made  machine,  and  comparisons  between  the 
two  are  likely  to  lead  to  incorrect  conclusions  concerning  the  organ- 
ism. The  machine  corresponds  more  closely  to  a  fully  developed 
morphological  part  of  the  organism  which  constitutes  a  definite 
functional  mechanism.  But  the  structure  and  function  of  such  a 
part  give  us  no  conception  of  the  organism  as  a  whole  and  of  its 
action  as  a  constructive  and  activating  agent. 

The  comparison  between  the  living  organism  and  the  man- 
made  machine  completely  ignores  the  relation  between  structure 
and  function  in  the  former.  And  any  conception  of  the  organism 
which  does  not  take  into  account  its  ability  to  construct  its  owti 
mechanism  is  very  far  from  adequate.  The  whole  living  organism 
may  be  compared  with  the  machine  plus  the  constructing  and 
activating  agent,  the  intelligence  that  makes  and  runs  it.  It  ma>- 
appear  at  first  glance  that  this  view  leads  necessarily  to  the  assump- 
tion that  an  intelligence  more  or  less  Uke  that  of  man  is  concerned 
in  the  development  of  every  organism.  This,  however,  is  far  from 
being  the  case.  In  the  broad  sense,  the  man  building  and  running 
a  machine  is  an  organism  constructing  a  part  with  a  detinite  func- 
tional mechanism  which  functions  under  the  control  of  the  whole. 

If  intelligence  is  a  function  of  the  human  or  any  other  organism, 
then  the  same  laws  must  hold  for  its  activity  as  for  that  of  organisms 


30  SENESCENCE  AND  REJUVENESCENCE 

in  general.  The  facts  show  clearly  enough  that  different  degrees 
of  intelligence  exist  in  different  organisms,  and  we  cannot  deny 
that  even  the  simple  organisms  show  something  remotely  akin 
to  intelligence.  On  the  other  hand,  many  of  the  supposed  funda- 
mental differences  between  the  organism  and  the  inorganic  world 
have  disappeared  in  the  light  of  scientific  investigation.  But 
even  supposing  that  we  shall  some  day  demonstrate  the  essential 
unity  of  the  universe  from  the  simplest  inorganic  system  to  the 
highest  organism,  when  that  is  done  there  is  no  reason  to  believe 
that  the  real  problem  of  teleology  will  be  eliminated ;  it  will  doubt- 
less still  be  before  us  as  a  problem  concerned,  not  with  any  single 
group  of  organisms,  nor  with  all  organisms,  but  with  the  world  as  a 
whole.  In  other  words,  on  the  basis  of  such  a  conception  there  is 
not  merely  an  analogy  but  a  fundamental  similarity  between  the 
river  with  its  current  and  channel,  the  organism  constructing  itself 
by  its  own  functional  activity,  and  the  man  constructing  and 
running  a  machine.  And  this  remains  true  whatever  the  final 
solution  of  the  teleological  problem. 

But  as  the  complex  structure  of  the  human  organism  and  also 
the  machine  which  it  has  constructed  have  constituted  essential 
factors  in  the  development  of  human  intelligence,  so  also  in  other 
organisms  the  approach  to  anything  hke  intelligence  in  the  broadest 
sense  is  manifestly  associated  with  the  development  of  structure. 
The  more  complex  the  structure,  particularly  of  the  nervous  sys- 
tem, the  closer  the  approach  to  intelligence.  This  is  again  merely 
a  special  case  under  the  general  relation  between  structure  and 
function:  the  more  complex  the  structure  the  greater  the  possi- 
bihties  of  function.  Moreover,  even  in  man  a  very  complex 
structure  is  developed  before  we  can  find  any  evidence  of  intelli- 
gence. In  short,  all  the  evidence  along  this  line  indicates  that 
anything  which  we  are  able  to  recognize  as  intelhgence  is  not  a 
primary  function  of  the  organism,  but  one  which  becomes  apparent 
only  in  a  highly  complex  structure.  Just  as  clearly  does  the  evi- 
dence indicate  that  there  is  no  real  break  in  the  series  between  the 
simplest  morphogenetic  activity  of  the  organism  and  the  man 
building  and  controlling  the  machine.  But  because  the  man  builds 
and  runs  the  machine  with  a  definite  purpose  in  mind,  it  does  not 


VARIOUS  THEORIES  OF  THE  ORGANISM  31 

at  all  follow  that  a  similar  idea  of  purpose  underlies  morphogenesis, 
even  though  the  dynamic  processes  may  be  more  or  less  similar  in 
both  cases.  The  foundations  from  which  purposive  action  arises 
must  be  sought  in  the  constitution  of  the  world  in  general,  but  it 
does  not  follow  that  purposive  action  is  everywhere  present. 

The  various  attempts  made  within  recent  years  to  interpret 
the  organism  in  terms  of  memory  (Semon,  '04),  behavior  (Schultz, 
'10,  '12),  entelechy  (Driesch,  '08),  or  other  more  or  less  psycho- 
logical or  teleological  terms,  are  interesting  to  every  biologist,  if 
only  as  indications  of  a  reaction  from  theories  current  a  few  years 
ago,  but  they  rather  obscure  than  illuminate  the  problem.  More- 
over, purposive  action  and  intelligence  in  various  degrees  of  com- 
plexity are  all  features  of  organic  Hfe,  but  any  attempt  to  show 
that  they  are  fundamental  or  universal  features  is,  to  say  the  least, 
premature  and  merely  a  matter  of  personal  opinion.  The  close 
association  between  complexity  of  structure  and  complexity  of 
behavior  in  organisms  should  lead  us  to  search  for  terms  common 
to  both,  rather  than  to  attempt  to  translate  either  into  terms  of 
the  other. 

REFERENCES 

Bechhold,  H. 

191 2.  Die  Colloide  in  Biologie  und  Medezin.    Dresden. 
Bredig,  G. 

1 90 1.    Anorganische  Fermente.    Leipzig. 
Child,  C.  M. 

191 1.  "A  Study  of  Senescence  and  Rejuvenescence  Based  on  Experiments 
with  Planarians,"  Arch.  f.  Entwickelungsmech.,  XXXI. 
Driesch,  H. 

1901.     Die  organischen  Regulationen.     Leipzig. 

1908.  The  Science  and  Philosophy  of  the  Organism,     London. 
Freundlich,  H. 

1909.  Kapillarchemie.     Leipzig. 
Graham,  T. 

1861.  "Liquid  Diflfusion  Applied  to  Analysis,"  Phil.  Trans.,  CLI. 

HOBER,  R. 

191 1.     Physikalische  Chemie  der  Zclle  und  dcr  Gewebe.     Dritte  Auflage. 
Leipzig. 

KtJSTER,  E. 

1913.  Uber  Zonenbildung  in  kolloidalcn  Mcdicn.    Jena. 


32  SENESCENCE  AND  REJUVENESCENCE 

Leduc,  S. 

1908.  "Essais  de  biologic  synthetique,"  Biochem.  Zeilschr.,  Festband  fiir 
H.  J.  Hamburger. 

igoga.  Les  Croissances   osmotiques  et  Vorigine   des  etres  vivantes.     Bar- 

le-Duc. 
19095.  "Les  bases  physiques  de  la  vie  et  la  biogenese,"  Presse  medicate, 

VII. 

1 9 10.  Theorie  physico-chimique  de  la  vie.     Paris. 

LlESEGANG,  R.  E. 

1909.  Beitrdge  zu  einer  Kolloidchemie  des  Lebens.    Dresden. 

1911.  "Nachahmung  von  Lebensvorgangen :  I,  Stoflverkehr,  bestimmt 
gerichtetes  Wachstum;  II,  Zur  Entwicklungsmechanik  des  Epi- 
thels,"  Arch.  f.  Entwickehmgsmech.,  XXXII. 

1914.  "Eine  neue  Art  gestaltender  Wirkung  von  chemischen  Aus- 
scheidungen,"  Arch.  f.  Entwickelungsmech.,  XXXIX. 

Mathews,  A.  P. 

1899.  "The  Changes  in  Structure  of  the  Pancreas  Cell,"  Jour.  ofMorph., 
XV  (Supplement). 

1905.  "A  Theory  of  the  Nature  of  Protoplasmic  Respiration  and 
Growth,"  Biol.  Bull.,  VIII. 

OsTWALD,  Wolfgang. 

191 2.  Grundriss  der  Kolloidchemie.    Dresden. 

Pfluger,  E.  F.  W. 

1875.  "tJber  die  physiologische  Verbrennung  in  den  lebendigen  Organ- 
ismen,"  Arch.},  d.  ges.  Physiol.,  X. 

RiGNANO,  E. 

1906.  Sur  la  Trasmissihilite  des  caracteres  acquis:  Hypothese  d'une  cen- 
troepigenese.     Paris. 

Roux,  W. 

1905.  "Die  Entwickelungsmechanik :  ein  neuer  Zweig  der  biologischen 
Wissenschaft,"  Vortr.  und  Aufs.  ii.  Entwickelungsmech.,  I. 

SCHULTZ,  E. 

1910.  Prinzipien  der  rationellen  vergleichenden  Emhryologie.     Leipzig. 
191 2.     "tJber    Periodizitat     und    Reize    bei   emigen    Entwicklungsvor- 

gangen,"  Vortr.  und  Aufs.  ii.  Entwickelungsmech.,  XIV. 

Semon,  R. 

1904.  Die  Mneme  als  erhaltendes  Prinzip  im  Wechsel  des  organischen 
Geschehens.    Leipzig. 

Verworn,  M. 

1903.    Die  Biogenhypothese.    Jena. 


VARIOUS  THEORIES  OF  THE  ORGANISM  ^^ 

Warburg,  O. 

1912a.  "Untersuchungcn  iibcr  die   Oxydationsprozesse  in  ZeUen      II  " 

Munchener  med.  Wochenschr.,  LVIII. 
1912b.  -VJhor  Beziehungen   zvvischen    Zellsiruktur    und    biochemischcn 

Keaktionen,    Arch.  f.  d.  gcs.  Physiol.,  CXLV 

1913.  Uber  die  Wirkung  der  Struktur  auf  chemische  Vorgdnge  in  Zcllcn 
Jena. 

1914.  "Uber  die  Empfindlichkeit  der  Sauerstoffatmung  gegeniiber  in- 
differenten  Narkotika,"  Arch.f.  d.  ges.  Physiol.,  CLVIII 

1914*.  "Beitrage  zur  Physiologic  der  Zelle,  insbesondere  iiber  die  Oxyda- 
tionsgeschwindigkeit  in  Zellen,"  Ergebji.  d.  Physiol.,  XIV. 
Zangger,  H. 

1908.     "liber   Membranen   und    Alembranfunktion,"   Ergebn    d    Phv 
siol.,   VII.  ■       ^ 


CHAPTER  II 

THE  LIFE  CYCLE 

GROWTH  AND  REDUCTION 

Definitions  of  growth  and  reduction. — One  of  the  most  charac- 
teristic and  striking  features  of  the  living  organism  is  its  abihty  to 
add  to  its  own  substance.  In  most  organisms  an  enormous  increase 
in  size  and  weight  occurs  during  the  earher  part  of  the  life  cycle. 
This  is  commonly  known  as  growth.  But  different  authorities  are 
not  entirely  agreed  as  to  what  constitutes  growth.  The  differ- 
ences of  opinion  seem  to  center  chiefly  about  the  question  whether 
growth  consists  simply  in  increase  in  size,  or  whether  change  in 
form  is  the  essential  feature.  Davenport/  following  Huxley  and 
others,  defines  organic  growth  as  increase  in  volume.  The  plant 
physiologist  Pfeffer  ('oi),  on  the  other  hand,  says  that  in  general 
all  formative  processes  which  lead  to  a  permanent  change  of  form 
are  to  be  regarded  as  growth.  Most  authorities  have  regarded  the 
addition  of  material,  or  of  certain  kinds  of  material,  or  the  increase 
in  size  as  the  essential  feature  of  growth.  To  make  change  of  form 
the  basis  of  growth  is  certainly  a  wide  departure  from  the  com- 
monly accepted  meaning  of  the  word,  and  also  fails,  I  think,  to 
recognize  the  significance  of  accumulation  of  material  in  the  organ- 
ism. Increase  in  size  or  the  addition  of  material  may  occur  without 
appreciable  change  in  form,  and  change  in  form  may  occur  without 
increase  in  size  or  amount  of  material,  and  most  of  those  who 
have  attempted  to  define  growth  have  recognized  this  fact.  The 
capacity  of  the  organism  to  add  to  its  own  substance  and  to  in- 
crease in  size  is  evidently  closely  connected  with  the  fundamental 
processes  of  metaboHsm,  and  even  organisms  which  do  not  undergo 
appreciable  changes  of  form  do  nevertheless  grow  in  the  usual 
sense  of  the  word. 

But  any  consideration  of  the  problem  of  growth  which  does 
not  take  into  account  the  process  of  reduction  is  incomplete.  Under 
the  usual  conditions  of  existence  the  healthy  active  organism  is  not 

I  In  Davenport's  Experimental  Morphology  ('97,  pp.  281-82)  a  number  of  the 
definitions  of  growth  which  have  been  given  are  cited. 

34 


THE  LIFE  CYCLE  35 

only  adding  new  material,  but  is  at  the  same  time  breaking  down 
and  eliminating  material  previously  accumulated.  The  total 
result  as  regards  size  or  bulk  is  simply  the  difference  between  the 
two  processes.  Some  of  the  substances  accumulated  within  the 
organism  break  down  less  rapidly  than  others,  but  even  such  sub- 
stances may  be  more  or  less  completely  removed.  In  the  more 
complex  organisms  also  some  of  the  substances  of  the  substratum 
are  apparently  more  stable,  i.e.,  inactive  chemically,  under  physio- 
logical conditions,  and  the  processes  of  breakdown  are  therefore 
less  conspicuous  as  a  factor  in  the  total  result  than  in  the  simpler 
forms.  Under  conditions  where  the  breakdown  of  material  over- 
balances the  increment,  as  for  example  in  starvation,  the  higher 
organisms  soon  die  with  a  considerable  portion  of  their  substance 
intact,  but  in  many  of  the  simpler  forms  the  material  previously 
accumulated  serves  to  a  large  extent  as  a  source  of  energy  and  the 
organism  remains  alive  and  active,  but  undergoes  reduction  until 
it  represents  only  a  minute  fraction  of  its  original  size.  Various 
species  of  the  flatworm  Planaria  may  undergo  reduction  from 
a  length  of  twenty-five  or  thirty  millimeters  (Fig.  i)  to  a  length 
of  three  or  four  millimeters  (Fig.  2)  with  a  corresponding  change 
in  other  proportions  before  they  die,  and  many  others  among 
the  simpler  organisms  are  capable  of  undergoing  great  reduc- 
tion without  death.  Since  the  addition  of  material  and 
increase  in  size  play  a  much  more  conspicuous  part  in  the  life  of 
organisms  in  nature,  and  particularly  in  the  higher  organisms, 
than  do  the  reductional  processes,  it  has  come  about  that  the  term 
growth  has  usually  been  applied  to  the  incremental,  or  productive, 
factors,  and  the  significance  of  reduction  in  the  life  cycle  has 
scarcely  been  considered. 

Various  authors  have  laid  stress  upon  the  permanency  of  the 
changes  involved  in  growth.  As  a  matter  of  fact,  these  changes 
are  not  necessarily  permanent,  although  they  are  more  stable  in 
the  higher  than  in  the  lower  organisms.  To  say  that  growth  con- 
sists in  permanent  increase  in  volume  or  change  of  form  is  to  ignore 
entirely  the  phenomena  of  reduction  which  are,  it  is  true,  most 
striking  in  the  lower  organisms,  but  which  may  occur  to  some 
extent  in  all. 


36 


SENESCENCE  AND  REJUVENESCENCE 


u 


Figs,  i,  2. — Planaria 
dorolocephala:  Fig.  i,  a 
well-fed  animal  25  mm.  in 
length;  Fig.  2,  an  animal 
reduced  by  starvation  from 
25  to  4  mm. 


Logically  our  definition  of  growth  might  well 
include  both  positive  and  negative  growth,  or 
production  and  reduction,  but  since  the  word 
growth  has  come  to  be  so  generally  associated 
with  an  increase  in  substance  it  is  perhaps 
inadvisable  to  attempt  to  change  its  meaning. 
We  may  then  retain  the  word  growth  for  posi- 
tive growth  or  production,  and  use  the  term 
reduction  for  negative  growth.  But  in  so  doing 
we  must  not  forget  that  both  these  processes 
are  in  the  broad  sense,  though  not  necessarily  in 
the  chemical  sense,  reversible,  and  that  any 
adequate  conception  of  the  relation  between 
the  substratum  and  the  dynamic  processes  in 
the  organism  must  be  based,  not  on  growth 
alone,  but  upon  both  growth  and  reduction. 
In  other  words,  the  activity  of  the  organism 
may  either  increase  or  decrease  the  amount  of 
its  substance  according  to  conditions. 

The  question  has  often  been  raised  whether 
the  increase  in  the  water-content  of  the  organism 
is  to  be  regarded  as  growth,  or  only  the  increase 
in  the  structural  substance.  Some  definitions 
of  growth  have  taken  the  one  view,  some  the 
other,  but  if  water  is  included  among  the  sub- 
stances concerned  in  growth  we  have  then 
to  determine  whether  increase  in  water- 
content  is  in  all  cases  to  be  regarded  as 
growth,  or  whether  we  shall  make  a  dis- 
tinction between  growth  and  passive  dis- 
tension due  to  external  factors.  Here 
again  views  differ.  As  a  matter  of  fact, 
various  investigators  have  shown  that  the 
imbibition  of  water  is  a  very  characteristic 
feature  during  at  least  certain  stages  of 
what  we  are  accustomed  to  call  growth: 
on    the    other   hand,   loss    of  water  is   a 


THE  LIFE  CYCLE  37 

characteristic  feature  of  certain  other  stages  of  the  life  cycle. 
Moreover,  there  is  evidence  that  water  is  produced  by  chemical 
action  in  the  organism  (Babcock,  '12),  and  it  is  a  familiar  fact 
that  water  is  absolutely  essential  to  life. 

But  an  adequate  definition  of  organic  growth  must  also  take 
account  of  the  fact  that  it  is  a  process  of  the  living  organism.  A 
passive  distension  of  the  organism  or  any  part  of  it  by  water 
or  other  substances,  or  a  passive  loss  of  water,  is  not  properly 
growth  or  reduction,  because  it  is  not  due  to  the  activity  of  the 
organism  or  part. 

If  we  admit  then,  first,  that  organic  growth  and  reduction  con- 
sist essentially  in  changes  in  the  amount  of  substance,  secondly, 
that  water  as  well  as  other  substances  may  be  involved  in  growth, 
and  thirdly,  that  growth  is  a  process  of  the  hving  organism,  our 
definitions  of  growth  and  reduction  must  read  somewhat  as  follows: 
organic  growth  is  an  increase,  organic  reduction  a  decrease,  in  the 
amount  of  the  substance  of  a  Hving  organism  or  part,  resulting 
directly  or  indirectly  from  its  specific  metabohc  activity.  This 
definition  does  not  any  more  than  others  avoid  all  difficulties,  for 
sharp  lines  of  distinction  do  not  necessarily  exist  in  natural  phe- 
nomena. Whether  we  call  a  certain  process  growth  or  not  must 
often  depend  upon  whether  we  are  considering  the  whole  organism 
or  a  part;  moreover,  it  is  impossible  to  separate  the  activity  of  the 
organism  completely  from  external  factors. 

Although  growth  in  its  simplest  terms  consists  in  large  measure 
in  the  synthesis  of  proteid  molecules,  it  is  evident  that  growth  is 
not  always  the  same  chemical  process.  Under  different  conditions 
different  proteid  molecules  may  be  formed,  and  very  often  growth 
results  from  the  synthesis  of  various  substances  other  than  proteids. 
Recent  investigations  seem  to  indicate  that  from  the  point  of  view 
of  nutrition  growth  in  recovery  from  starvation  is  not  the  same  as 
developmental  growth  with  continuous  feeding  and  that  growth  in 
adult  life  is  not  the  same  as  growth  during  youth.'  Doubtless 
many  other  differences  will  appear  as  investigation  proceeds,  but 
there  seems  at  present  to  be  no  adequate  reason  for  limiting  the 

'  See  the  papers  by  Osborne  and  Mendel,  in  the  references  appended  to  chap,  xi, 
particularly  the  recent  general  discussion  of  the  subject  by  Mendel  ('14)- 


38  SENESCENCE  AND  REJUVENESCENCE 

term  growth  to  one  or  the  other  of  the  particular  processes  as  some 
authors  incline  to  do.  Growth  results  primarily  from  the  ability 
of  the  cell  to  synthesize  certain  substances  which,  once  formed, 
remain  as  relatively  permanent  constituents  of  the  cell.  Under 
different  conditions  the  nutritive  substances  necessary,  the  course 
of  synthesis,  and  the  substances  formed  must  differ  widely,  but 
growth  is  a  complex  organic  process  rather  than  this  or  that  par- 
ticular chemical  reaction. 

The  nature  of  growth  and  reduction. — The  question  why  the 
organism  grows  is  one  of  great  interest,  and  while  we  cannot  at 
present  answer  it  fully,  we  can  at  least  reach  certain  provisional 
conclusions.  On  the  basis  of  the  chemical  hypothesis  of  the  labile 
proteid  molecule,  growth  remains  a  mystery.  We  cannot  conceive 
how  these  labile  molecules  are  able  to  build  up  others  hke  them- 
selves. Reduction,  however,  is  readily  enough  accounted  for 
as  the  result  of  breakdown  of  the  labile  molecules.  But  if  we 
regard  the  organism  as  a  complex  of  reactions  in  a  colloid  sub- 
stratum, the  problem  of  growth  assumes  a  different  form  and  is 
open  to  attack.  Certain  aspects  of  the  problem  require  brief  con- 
sideration from  this  point  of  view. 

The  reversibihty  of  the  growth  process  leads  us  at  once  to  ask 
whether  or  to  what  extent  reversible  chemical  reactions  are  con- 
cerned. If  we  could  regard  growth  and  reduction  as  the  two 
terms  of  a  reversible  chemical  reaction  it  would  simphfy  our  con- 
ceptions very  greatly.  Unfortunately,  however,  this  seems  to  be 
impossible.  Reversible  chemical  reactions  are  undoubtedly  con- 
cerned in  the  synthesis  and  breakdown  of  the  various  molecules 
which  make  up  protoplasm,  but  the  growth-reduction  process  is 
something  more  than  such  a  reaction.  Apparently  the  course  of 
synthesis  and  of  breakdown  and  the  character  of  the  end  products 
may  differ  widely.  Many  or  all  of  the  component  reactions  in 
growth  and  reduction  may  be  reversible,  but  it  does  not  by  any 
means  follow  that  reduction  is  a  reversal  in  the  chemical  sense  of 
growth.  During  a  considerable  part  of  Hfe  under  the  usual  condi- 
tions the  synthesis  of  certain  substances  overbalances  their  break- 
down, they  accumulate  in  the  organism,  and  growth  occurs. 
Evidently  conditions  in  the  organism  are  such  that  certain  sub- 


THE  LIFE  CYCLE  39 

stances  once  formed  are  not  as  readily  or  as  rapidly  decomposed 
and  eliminated. 

It  is  evident  that  synthesis  of  proteid  molecules  is  a  factor  of 
great  importance  in  growth,  since  proteids  form  the  chief  constitu- 
ents of  protoplasm,  but  there  is  no  reason  to  believe,  as  various 
authorities  have  maintained,  that  the  metabolic  process  consists 
wholly  or  chiefly  in  the  synthesis  and  decomposition  of  proteid 
molecules.  All  the  facts  indicate  that  much  of  the  energy  of  the 
organism  comes  from  substances  other  than  proteids,  and  that  pro- 
teid synthesis  is  only  one  of  many  chemical  transformations  occur- 
ring in  the  organism. 

Moreover,  according  to  physico-chemical  laws,  the  accumulation 
of  colloids  and  other  substances  as  a  substratum  in  the  organism  or 
in  the  cell  must  depend  upon  what  we  may  call  their  physiological 
stability.  A  physiologically  stable  substance  is  one  which,  when 
once  formed,  cannot  readily  escape  from  the  living  cell  or  organism 
under  the  existing  conditions,  unless  it  undergoes  chemical  change, 
and  which,  under  the  usual  physiological  conditions,  does  not  under- 
go this  change  or  undergoes  it  less  readily  than  other  substances. 
Physiological  stability  depends  then,  not  only  on  the  constitution 
of  the  substance  concerned,  but  also  and  probably  to  a  large  extent 
on  the  conditions  to  which  it  is  subjected.  Different  substances 
differ  in  stability  under  the  same  conditions,  and  the  same  substance 
may  differ  very  greatly  in  stability  under  different  conditions. 
Moreover,  physiological  stabihty  does  not  necessarily  imply  com- 
plete chemical  stabihty.  There  is  good  reason  to  believe  that 
many  substances  in  the  cell  are  undergoing  more  or  less  continuous 
partial  chemical  breakdown  and  reconstitution,  but  so  long  as  they 
do  not  undergo  complete  breakdown  and  elimination  they  consti- 
tute parts  of  the  cell  which  are  relatively  stable  physiologically. 
In  most  plants,  for  example,  proteid  molecules  once  formed  never 
undergo  decomposition  to  the  point  where  the  nitrogen  which  they 
contain  is  ehminated  in  any  form,  yet  there  can  be  no  doubt  that 
these  proteids,  or  some  of  them,  take  part  in  the  chemical  reactions 
within  the  cell  and  that  their  molecules  are  often  partially  decom- 
posed and  reconstituted.  They  are  then  physiologically,  though 
not  necessarily  chemically,  stable  constituents  of  the  plant  cell. 


40  SENESCENCE  AND  REJITV'ENESCENCE 

The  visible  substratum  of  the  organism,  i.e.,  the  protoplasm, 
must  consist  fundamentally  of  such  physiologically  stable  sub- 
stances, for  if  this  were  not  the  case  we  should  have  merely  a  system 
of  chemical  reactions,  and  no  permanency  of  form  or  structure 
could  exist.  Theoretically,  at  least,  a  distinction  must  be  made 
between  the  substratum  of  the  cell  or  organism  and  the  substances 
which  are  decomposed  and  eliminated  and  which  constitute  the 
source  of  energy.  Practically,  however,  such  a  distinction  cannot 
be  clearly  made  in  most  cases,  for  physiological  stability  is  relative 
rather  than  ^.bsolute  and  it  is  impossible  to  say  in  a  given  case  to 
what  extent  the  substratum  is  itself  involved  in  the  chemical  re- 
actions. Still  it  is  evident  that  the  substances  which  accumulate 
within  the  cell  under  given  conditions  as  its  visible  or  structural 
substratum  must  be  in  general  and  under  the  existing  conditions 
less  subject  to  decomposition  into  ehminable  form  than  those  sub- 
stances which  undergo  breakdown  and  elimination. 

The  organic  colloids  are  in  general  physiologically  stable  sub- 
stances. When  once  formed  within  the  cells  they  do  not  diffuse 
readily  and  cannot  ordinarily  escape  except  as  they  are  decomposed 
into  eliminable  substances.  We  know  from  studies  of  the  metabo- 
lism of  the  higher  animals  and  from  the  amount  of  nitrogen- 
containing  food  which  is  necessary  for  maintenance  that  in  these 
forms  at  least  the  breakdown  of  proteid  molecules  into  completely 
eliminable  form  constitutes  only  a  fraction  of  the  metabolic  process 
at  any  given  time.  Moreover,  some  of  the  nitrogenous  substances 
excreted  may  come  from  proteids  of  the  food  which  have  been 
decomposed  without  forming  a  part  of  the  substratum  of  the  cells. 
Undoubtedly  also  many  chemical  changes  occur  in  the  colloid 
substratum  which  involve  merely  the  transformation  or  exchange 
of  certain  chemical  groups  and  not  the  complete  disruption  of  the 
molecule.  Chemical  changes  of  this  sort  do  not  necessarily  involve 
the  disintegration  of  the  substratum  as  a  whole,  and  it  is  probable 
that  cellular  structures  are  often  the  seat  of  such  changes  without 
undergoing  any  conspicuous  morphological  change. 

The  fact  that  emulsoid  colloids  and  particularly  proteids  are 
the  fundamental  constituents  of  the  substratum  of  living  organisms 
is  a  necessary  consequence,  first,  of  the  formation  of  these  substances 


THE  LIFE  CYCLE  41 

in  the  course  of  the  reactions  which  constitute  metaboHsm,  and, 
secondly,  of  their  physico-chemical  properties.  The  substratum 
once  formed  in  the  course  of  chemical  reactions  affords  a  basis  for 
the  continuation  of  the  reactions  and  for  the  further  addition  of 
colloids.  So  far  as  the  metabolic  reactions  are  enzyme  reactions, 
the  structural  substratum  of  the  organism  must  consist  of  the  sub- 
stances which  for  one  reason  or  another  are  less  susceptible  to 
enzyme  action  than  other  substances  which  are  transformed  without 
forming  a  part  of  the  structure. 

According  to  this  view  the  colloid  substratum  and  the  morpho- 
logical structure  of  the  organism  represent,  so  to  speak,  the  sedi- 
ment from  the  metabolic  process.  They  are,  in  short,  by-products 
of  the  reactions  which  do  not  readily  escape  from  the  cell  unless 
they  undergo  decomposition  and  which  are  relatively  stable. 
Therefore  they  must  constitute  the  more  permanent  constituents 
of  the  cell  and  appear  as  a  visible  substratum  or  more  or  less  perma- 
nent structure  of  some  sort.  The  constitution  of  the  structural 
substratum  developed  in  different  organisms  differs  because  the 
metabolic  processes  and  the  substratum  already  existing  at  the 
beginning  of  development  differ.  The  visible  organism  is  then 
the  sediment  left  behind  by  the  metabolic  current:  it  consists  of 
the  substances  which  the  current  is  unable  to  carry  farther.  It  does 
not  represent  life  any  more  than  the  sand-bar  represents  the  river; 
it  is  simply  a  product  of  past  activity  which  may  influence  future 
activity.  Sixty  years  ago  Huxley  said  concerning  the  cells:  ''  They 
are  no  more  the  producers  of  the  vital  phenomena  than  the  shells 
scattered  along  the  sea-beach  are  the  instruments  by  which  the 
gravitative  force  of  the  moon  acts  upon  the  ocean.  Like  these, 
the  cells  mark  only  where  the  vital  tides  have  been  and  how  they 
have  acted"  (Huxley,  '53).  And  yet  since  Huxley's  words  were 
written  how  many  attempts  have  been  made  either  to  show  that 
this  or  that  structural  element  of  the  organism  represents  some- 
thing fundamental  to  life  or  to  translate  the  phenomena  of  life 
into  terms  of  an  invisible  hypothetical  structure! 

The  visible  structural  features  of  the  organic  substratum  possess 
very  different  degrees  of  stability:  some  are  evanescent,  while 
others  persist  throughout  the  life  of  the  cell  in  which  they  arise. 


42  SENESCENCE  AND  REJUVENESCENCE 

This  is  true,  not  only  as  regards  the  different  structures  in  a  cell, 
but  also  as  regards  different  cells  of  an  organism,  and  the  cells  of 
different  organisms.  Many  of  the  more  or  less  evanescent  struc- 
tural appearances  in  protoplasm  are  perhaps  nothing  more  than 
visible  indications  of  differences  in  the  aggregations  of  the  colloid. 
The  more  highly  aggregated  portions,  which  form  more  or  less 
dense  colloid  gels,  appear  as  more  or  less  definite  structures,  the  less 
aggregated  portions  as  indefinitely  granular,  alveolar,  or  fluid.  But 
even  in  such  cases  the  denser  portions  of  the  protoplasm  are  probably 
for  the  time  being  less  subject  to  chemical  change  than  the  more 
fluid  portions  because  of  their  physical  condition.  It  is  evident, 
however,  that  many  of  the  more  permanent  structural  features 
result  from  the  accumulation  in  the  cell  of  specific  substances 
which  possess  a  relatively  high  degree  of  physiological  stability 
under  the  existing  conditions.  But  there  is  little  doubt  that  in  at 
least  most  organic  structures  which  are  not  mere  inclosures  in  the 
protoplasm  or  extra-cellular  secretions  a  greater  or  less  degree  of 
chemical  breakdown,  of  degradation  of  the  structural  substance,  is 
more  or  less  constantly  occurring  while  life  continues.  In  some 
cases  this  may  be  very  slight  in  amount  or  may  involve  only  certain 
components,  in  others  it  may  involve  the  whole  structural  basis 
of  the  organ  or  organism.  When  the  conditions  are  such  that  the 
new  material  added  exceeds  in  amount  that  undergoing  breakdown, 
growth  occurs,  but  when  the  rate  of  breakdown  exceeds  that  of 
accumulation,  reduction  is  the  result. 

According  to  the  theory  of  the  labile  proteid  molecule,  func- 
tional activity  results  primarily  from  the  breakdown  of  the  struc- 
tural substratum  itself,  or  at  least  of  its  proteid  constituents. 
But  if  the  substratum  consists  of  comparatively  stable  by-products 
of  metaboHsm,  as  the  facts  seem  to  indicate,  then  it  is  clear  that 
the  energy  of  functional  activity  must  ordinarily  come  chiefly  from 
other  sources,  i.e.,  from  the  breakdown  of  other  substances  which 
do  not  constitute  an  essential  structural  part  of  the  protoplasm. 
Under  the  usual  conditions  the  structural  substratum  is  probably 
to  a  large  extent  a  field  in  which  the  reactions  occur  rather  than 
the  reacting  substance  or  substances,  but  in  the  absence  of  other 
nutritive  substances,  i.e.,  in  starvation,  it  may  itself  become  the 


THE  LIFE  CYCLE  43 

chief  source  of  energy,  especially  in  the  lower  animals.  As  already 
pointed  out,  different  constituents  of  the  substratum  show  ver>' 
different  degrees  of  stability,  some  being  evanescent  and  disappear- 
ing at  once  with  slight  change  in  conditions,  while  others  once 
formed  persist  for  a  long  time  or  through  life.  It  is  therefore 
impossible  to  distinguish  sharply  between  what  constitutes  the 
substratum  and  what  does  not.  We  can  only  say  that  the  sub- 
stratum consists  in  general  of  more  stable  substances  than  those 
which  do  not  appear  in  it. 

As  our  knowledge  of  the  great  complex  of  reactions  which  we 
call  metabolism  increases,  it  becomes  more  and  more  evident  that 
the  different  reactions  of  the  complex  are  not  entirely  independent 
of  each  other,  but  constitute  a  reaction  system.  In  this  system  the 
oxidations  appear  to  be  the  most  important  or  dominant  factor,  the 
independent  variable,  as  Loeb  and  Wasteneys  ('11)  express  it,  upon 
which  the  other  reactions  depend  more  or  less  closely.  Rate  of 
oxidation  is  a  more  fundamental  factor  in  growth  than  the  amount 
of  nutritive  material  in  excess  of  a  certain  minimum.  From  this 
point  of  view  the  term  "metabolism"  loses  some  of  its  vagueness. 
It  is  not  simply  a  hodgepodge  of  chemical  reactions  in  which  now 
one,  now  another,  component  is  most  conspicuous,  as  external  con- 
ditions change,  but  rather  an  orderly  correlated  series  of  events  in 
which  certain  reactions  play  the  leading  roles.  The  rate  or  char- 
acter of  component  reactions  may  change  very  widely  with  external 
conditions,  but  nevertheless  the  reaction  system  retains  in  general 
certain  definite  characteristics  and  the  relation  between  its  com- 
ponent reactions  persists.  Anabolism  and  katabolism,  the  synthesis 
and  the  breakdown  of  the  substance  of  organisms,  are  not  independ- 
ent processes,  but  the  syntheses  are  apparently  associated  with, 
and  in  greater  or  less  degree  dependent  in  some  way  upon,  the 
oxidations. 

From  this  point  of  view  functional  h^-pertrophy  loses  its  peculiar 
character.  It  is  not  in  any  sense  a  "regeneration  in  excess"  or  an 
"over-compensation,"  as  it  is  so  generally  assumed  to  be,  but  is 
simply  the  result  of  increased  metabolism  in  the  presence  of  an 
adequate  nutritive  supply.  Increased  metabohsm  under  these 
conditions  means  increased  production  of  structural  substances. 


44  SENESCENCE  AND  REJUVENESCENCE 

The  organism  does  not  construct  itself /or  function  as  the  vitalistic 
and  chemical  theories  maintain:  it  constructs  itself  by  function. 
When  the  supply  of  nutritive  material  from  without  is  insuffi- 
cient, the  previously  accumulated  structural  material  may  serve 
as  a  source  of  energy  to  a  much  greater  extent  than  when  nutritive 
material  is  present  in  excess,  and  under  these  conditions  the  new 
structural  material,  if  any  is  formed,  may  be  insufficient  to  cover 
the  loss  and  reduction  results.  Such  reduction  may  involve  the 
whole  organism  to  a  greater  or  less  extent,  as  in  the  flatworms  and 
other  simple  animals,  or  it  may  involve  only  or  chiefly  certain  parts, 
but  in  all  cases  we  find  that  some  parts  or  substances  are  involved 
to  a  greater  extent  than  others.  In  a  starving  flatworm,  for 
example,  certain  organs  may  disappear  entirely  before  death  occurs, 
while  others  retain  more  nearly  their  usual  proportions.  Much 
has  been  made  of  this  fact  in  a  teleological  sense  (see,  for  example, 
E.  Schultz,  '04),  and  it  has  been  repeatedly  pointed  out  that  the 
organs  least  affected  are  those  most  essential  to  the  life  of  the 
organism.  But  a  teleological  interpretation  seems  to  be  quite 
unnecessary.  In  general  it  is  very  evidently  the  case  that  those 
organs  which  are  most  constantly,  most  frequently,  or  most  in- 
tensely active  in  the  life  of  the  organism  undergo  least  reduction 
during  starvation.  There  is  some  reason  to  believe  that  the 
structural  substratum  of  the  cells  of  such  organs  is  more  stable  than 
that  of  cells  which  possess  in  general  a  low  rate  of  metaboHsm.  The 
nervous  system  undergoes  least  reduction  during  starvation,  and 
during  the  earher  stages  of  development  it  certainly  has  the  highest 
metabohc  rate  of  any  part  of  the  body,  and  in  many  cases,  if  not 
in  all,  this  condition  persists  throughout  Hfe.  Furthermore,  during 
the  later  stages  of  Hfe  its  special  functional  activity  is  certainly 
almost  if  not  quite  continuous.  In  such  organs  energy  must  be 
derived  to  a  much  greater  extent  from  nutritive  substances  than 
from  the  substratum  of  the  cells  itself.  Consequently,  during 
starvation  their  losses  are  less  and  are  more  completely  repaired 
than  in  organs  where  the  substratum  is  less  stable.  Thus  the  more 
active  and  therefore  the  more  persistent  organs  maintain  them- 
selves largely  at  the  expense  of  other  less  active  parts  in  which  the 
degradation  of   the  structural  substratum  occurs  more  readily. 


THE  LIFE  CYCLE  45 

And  it  is  these  more  continuously  or  more  intensely  active  organs 
which  are  more  essential  to  life.  But  according  to  this  view  they 
undergo  less  reduction  in  starvation,  not  because  they  are  more 
essential  in  life,  but  because  they  are  more  active. 

Reduction  in  an  organ  or  part  may  also  occur  when  conditions 
change  so  that  a  decrease  in  the  average  rate  of  its  metabolism  below 
a  certain  level  occurs  and  synthesis  of  structural  substances  does  not 
compensate  the  gradual  loss.  The  atrophy  of  organs  from  disuse 
is  a  case  in  point.  And,  finally,  reduction  may  occur  in  a  part 
when  the  correlative  conditions  which  were  an  essential  factor  for 
its  continued  existence  as  a  part  undergo  change.  In  such  cases 
it  is  difficult  to  determine  whether  the  change  in  metaboHsm  is 
primarily  qualitative  or  quantitative.  In  the  lower  organisms 
extensive  reduction  of  this  kind  occurs  when  pieces  are  isolated 
and  undergo  reconstitution.  Previously  existing  organs  may  be 
reduced  and  disappear  and  others  be  formed  anew.  In  the  higher 
organisms  such  processes  of  reduction  are  narrowly  limited. 

If  we  accept  the  general  conception  of  growth  and  reduction 
here  outlined,  then  it  is  no  longer  necessary'  to  assume  the  existence 
of  a  mysterious  growth-impulse  which  gradually  decreases  in  inten- 
sity during  development,  for  growth  is  primarily  the  accumulation 
of  certain  substances  formed  in  the  course  of  the  metaboUc  reactions 
which  are  physiologically  more  stable  than  other  substances  that 
break  down,  furnish  energy,  and  are  eliminated.  Reduction 
occurs  when  the  breakdown  and  elimination  of  the  ceU  substance 
is  not  balanced  by  the  synthesis  of  new  substance.  Some  such 
conception  of  growth  and  reduction  seems  to  be  forced  upon  us  by 
the  facts,  for  certainly  there  is  every  reason  to  believe  that  the 
different  constituent  substances  of  the  cell  show  very  dilTerent 
degrees  of  stabihty  and  that  the  stability  of  a  given  substance  may 
differ  with  different  conditions.  Organic  growth  remains  a  com- 
plete mystery  unless  certain  fundamental  constituents  of  proto- 
plasm are  relatively  stable  under  the  conditions  of  their  production 
in  the  cell. 

DIFFERENTIATION  AND  DEDIFFERENTLA.TION 

Diferentiation. —The  process  of  development  in  the  organism 
is  also  a  process  of  differentiation,  of  apparent  complication,  but 


46  SENESCENCE  AND  REJUVENESCENCE 

we  find  that  differences  in  reaction  or  in  capacity  to  react  very 
commonly  exist  in  different  parts  even  before  visible  differentiation 
occurs,  or  in  cases  where  it  never  occurs.  The  term  "specifica- 
tion" is  often  used  for  these  differences  which  appear  only  in 
physiological  activity,  and  "differentiation"  for  the  visible  struc- 
tural differences.  The  distinction  is  of  course  arbitrary,  for  the 
visible  differences  result  from  differences  in  physiological  activity. 
An  orderly  sequence  of  differentiation  during  development  is 
characteristic  of  at  least  all  except  the  very  simplest  organisms  and 
probably  in  these  also  some  degree  of  differentiation  exists. 

In  its  biological  sense  the  term  "differentiation"  is  purely 
descriptive:  broadly  speaking,  differentiation  includes  all  per- 
ceptible changes  in  structure  or  behavior  from  the  primitive  embry- 
onic or  "undifferentiated"  condition,  which  occur  either  in  the 
cells  or  parts  of  an  organism  during  its  developmental  history,  or 
in  different  organisms  in  the  course  of  evolution.  It  is,  in  short, 
a  becoming  different,  but  since  the  process  of  becoming  different 
in  cells  and  organisms  is  a  change  from  a  generalized  to  a  specialized 
condition — a  progressive  development  of  particular  kinds  of  struc- 
ture and  activity  in  different  parts  of  the  whole — differentiation  in 
organisms  is  a  process  of  specialization. 

The  problem  of  differentiation  has  long  been  one  of  the  great 
biological  problems.  Biological  thought  has  always  been  divided 
upon  the  question  of  preformation  versus  epigenesis.  To  what 
extent  does  the  differentiation  of  the  fully  developed  organism 
actually  exist  as  something  preformed  in  the  germ,  so  that  develop- 
ment is  strictly  an  unfolding,  a  becoming  visible,  of  what  already 
exists,  and  to  what  extent  is  there  a  real  increase  in  complexity 
during  development?  The  corpuscular  theories  are  an  attempt 
to  answer  the  question  from  the  point  of  view  of  preformation,  but 
they,  Hke  the  vitalistic  theories,  succeed  merely  in  placing  the  prob- 
lem beyond  the  reach  of  investigation.  It  is  evident  that  if  the 
organism  is  a  physico-chemical  system,  at  least  some  differentiations 
must  arise  in  the  course  of  development.  The  adult  organism  is 
represented,  not  in  the  morphological  structure  nor  in  the  physical 
and  chemical  changes  of  the  reproductive  cell  or  cell-mass,  but 
rather  in  its  capacities.     The  experimental  investigation  of  recent 


THE  LIFE  CYCLE  47 

years  has  shown  that  different  degrees  of  differentiation  exist  in 
different  reproductive  cells,  but  has  not  afforded  any  real  support 
to  the  view  that  the  morphological  characters  of  the  adult  are 
represented  in  some  way  by  distinct  entities  in  the  germ.'  Hut 
even  if  we  admit  that  organic  differentiation  is,  at  least  to  a  large 
extent,  an  epigenetic  process,  the  real  problem  still  remains.  The 
orderly  and  definite  character  of  the  process,  the  variety  of  struc- 
tural features,  and  their  apparent  adaptation  to  the  function  which 
they  are  to  perform,  all  combine  to  render  the  problem  one  of  the 
greatest  interest  and  significance. 

At  present,  however,  it  must  suffice  to  call  attention  only  to 
certain  aspects  of  the  problem.  In  the  first  place,  in  so  far  as 
differentiation  is  really  a  progressive  or  epigenetic  process,  it  must 
depend  on  changes  of  some  sort  in  the  dynamic  processes  in  different 
regions  of  the  developing  organism.  We  know  that  differentiation 
in  its  specific  features  is  to  a  large  extent  independent  of  external 
conditions;  therefore  the  internal  conditions  must  determine  these 
changes.  And  this  brings  us  to  the  important  question:  How 
can  such  localized  differences  in  the  dynamic  processes  arise  in  the 
developing  organism  ?  The  corpuscular  theories  have  accustomed 
us  to  regard  different  morphological  parts  of  the  organism  as 
qualitatively  different,  and  it  is  evident  that  in  many  cases  they 
are,  but  it  does  not  necessarily  follow  that  the  qualitative  differences 
are  primary,  or  that  all  differentiations  are  quahtative.  It  is  a  well- 
known  fact  that  quantitative  differences  in  the  conditions  existing 
in  a  chemical  reaction  may  result  in  quahtatively  different  products, 
and  this  is  demonstrated  for  many  reactions  which  occur  in  the 
metabohc  complex.  It  cannot  then  be  doubted  that  qualitative 
differences  may  result  from  quantitative  differences  in  the  processes 
occurring  in  the  organism.  We  also  know  that  many  morpho- 
logical differences  are  differences  of  size,  shape,  or  quantity  of  some 

'  In  view  of  the  present  vogue  of  the  factorial  hypothesis  among  investigators 
in  the  field  of  genetics,  and  particularly  of  certain  attempts  to  apply  it  to  the  chromo- 
somes, such  a  statement  may  appear  to  many  as  at  least  unwarranted,  if  not  incorrect. 
The  factorial  hypothesis,  however,  does  not  necessarily  involve  the  assumption  of 
factors  as  distinct  entities  in  the  germ,  and  the  attempts  to  connect  particular  factors 
with  particular  chromosomes  or  parts  of  chromosomes  are  not  at  present,  properly 
speaking,  scientific  hypotheses. 


48  SENESCENCE  AND  REJUVENESCENCE 

other  kind,  which  are  not  necessarily  quahtative  in  any  sense. 
And,  finally,  we  are  able  to  determine  experimentally  the  devel- 
opment of  very  different  morphological  characters  by  changes  in 
conditions  which  affect  primarily  the  rate  and  not  the  character 
of  the  metabolic  reactions  (Child,  'ii).  To  what  extent  quantita- 
tive dift'erences  in  the  dynamic  processes  actually  serve  as  a  basis 
for  speciahzation  and  differentiation  we  do  not  know,  although  it 
is  certain  that  they  are  a  much  more  important  factor  than  most 
biologists  have  been  accustomed  to  believe. 

But,  supposing  that  quantitative  or  qualitative  differences 
arise  or  exist  in  different  regions  of  the  developing  organism,  how 
can  they  persist  in  a  substance  of  the  physical  consistency  of  pro- 
toplasm ?  It  is  here  that  the  colloid  condition  of  the  substratum 
plays  a  very  important  part.  The  organic  colloids  with  their 
sUght  diffusibility,  their  effect  on  the  diffusion  of  other  substances, 
their  viscosity  and  differences  of  aggregate  condition,  afford  possi- 
bilities for  the  localization  as  well  as  the  origination  of  different 
processes  which  do  not  exist  in  any  other  known  medium.  The 
experiments  on  the  production  of  form  and  structure  by  means  of 
chemical  reactions  in  a  colloid  substratum  outside  the  organism 
demonstrate  how  readily  even  complex  morphological  features 
may  arise  under  such  conditions,  and  in  such  cases  we  are  often 
able  to  analyze  the  process  of  differentiation.  We  have  then  in  the 
colloid  substratum  a  real  basis  for  differentiation,  and  the  problem 
of  morphogenesis  becomes  accessible  to  scientific  investigation  and 
analysis,  instead  of  being  merely  restated  in  terms  of  some  "vital- 
istic"  principle  or  of  determinants  or  other  ultimate  units. 

The  embryonic  or  undifferentiated  cell  is  distinguishable  from 
the  speciaHzed  or  differentiated  cell  rather  by  the  absence  than  by 
the  presence  of  definite  morphological  features.  It  represents  the 
cell  of  the  species  reduced  to  its  simplest  morphological  terms, 
consisting  essentially  of  nucleus  and  relatively  homogenous  cyto- 
plasm.^    It  is  of  course  true  that  cells  which  are  not  morphologically 

■  Embryonic  cells  are  shown  in  Fig.  113  (p.  285),  and  in  the  smaller  cells  of  Fig. 
187  Cp.  347),  and  in  Fig.  194,  em  (p.  348).  Cells  which  are  embryonic  in  appear- 
ance are  represented  more  or  less  diagrammatically  in  various  other  figures,  e.g., 
Figs.  71-74  (pp.  206,  208)  and  Fig.  192,  pc  (p.  348). 


THE  LIFE  CYCLE  49 

different  in  any  visible  way  may  show  themselves  by  their  behavior 
to  be  physiologically  different,  so  that  the  absence  of  visible  differ- 
entiation in  the  cell  is  not  proof  that  the  cell  is  completely  unspecial- 
ized. 

The  substance  of  the  undifferentiated  cell  is  the  general  meta- 
bohc  substratum  of  the  organism,  and  it  is  the  chemical  or  physical 
transformations  of  this  substratum,  or  the  addition  of  substances 
to  it,  that  constitutes  morphological  differentiation.  Physiological 
differentiation  consists  in  the  progressive  development  of  certain 
activities  at  the  expense  of  others. 

While  we  know  too  Httle  at  present  of  the  nature  of  the  various 
metaboHc  processes  and  of  the  relation  between  metabohsm  and 
the  cellular  substratum  to  permit  us  to  reach  positive  conclusions 
concerning  the  nature  of  dift'erentiation,  the  facts  at  hand  suggest 
certain  probabilities.     In  the  first  place  the  embryonic  cell  very 
evidently  has  in  general  a  higher  metabolic  rate,  or  capacity  for 
a  higher  rate,  independent  of  external  stimulation,  than  do  differ- 
entiated cells.     Apparently  the  mere  continuation  of  Hfe  in  the 
cell  without  cell  division  brings  about  changes  which  decrease 
the  metabohc  rate.     Such  changes  may  conceivably  result  from 
gradual  atomic  rearrangements  or  from  changes  in  aggregate  con- 
dition of  the  colloids.     It  is  a  well-known  fact  that  emulsoid  sols 
outside  the  organism  undergo  slow  changes  in  the  direction  of 
coagulation,  even  when  kept  under  as  nearly  as  possible  constant 
conditions,  and  there  is  good  reason  to  beheve  that  similar  changes 
occur  in  the  colloids  of  the  living  organism.     In  the  coagulation 
of  proteids  by  high  temperatures  time  is  a  factor,  i.e.,  the  occurrence 
of  coagulation  depends,  not  only  upon  the  actual  temperature,  but 
on  the  time  of  exposure  to  it:  the  lower  the  temperature,  the  longer 
the  time  necessary  to  bring  about  perceptible  coagulation.     From 
the  character  of  this  relation  between  time  of  exposure  and  tem- 
perature it  is  inferred  that,  theoretically,  coagulation  must  occur 
at  all  temperatures  above  the  freezing-point  of  the  sol,  its  rate  being 
infinitely  slow  at  low  temperatures  and  increasing  rapidly  as  the 
temperature  rises.     The  fact  that  coagulation  changes  do  occur 
slowly  in  colloid  sols  at  ordinary  room  temperatures  supports  this 
view.     Lepeschkin    ('12)    has   found    that    the    relation    between 


50  SENESCENCE  AND  REJUVENESCENCE 

temperature,  time  of  exposure,  and  occurrence  of  coagulation  as 
indicated  by  death  is  the  same  in  Hving  plant  cells  as  in  proteid 
sols  outside  the  organism,  and  he  therefore  concludes  that  the  pro- 
toplasmic sol  is  slowly  undergoing  changes  in  the  direction  of  coagu- 
lation even  at  temperatures  where  continued  life  is  possible.  If 
this  view  is  correct,  then  a  slow  increase  in  aggregation  is  occurring 
continuously  in  protoplasm,  but  the  formation  of  new  sol  and  the 
gradual  chemical  breakdown  of  the  older  partially  coagulated  sub- 
stance may  serve  to  delay  the  final  result  for  a  long  time,  or  indefi- 
nitely. 

The  accumulation  and  apparent  gelification  of  protoplasm  in 
the  course  of  growth  and  differentiation  suggest  that  changes  of 
this  sort  are  characteristic  of  the  developmental  history  of  all 
organisms.  If  this  is  true,  they  must  result  in  increasing  physio- 
logical stability  of  the  protoplasm  or  parts  of  it,  and  so  lead  to 
decrease  in  the  rate  of  metabolism,  and  the  decrease  in  metabolic 
rate  may  in  time  lead  to  changes  in  the  character  of  the  metabolic 
complex  and  so  to  further  changes  in  structure  which  may  again 
alter  metabolic  conditions,  and  so  on. 

It  is  probable  then  that  mere  continued  existence  may  in  many 
cases  result  in  gradual  progressive  changes  in  protoplasm  which 
become  evident  sooner  or  later  as  some  degree  and  kind  of  differ- 
entiation. Such  a  process  is  a  self-differentiation  in  the  strictest 
sense.  Its  occurrence  or  non-occurrence  must  depend  upon  the 
absence  or  presence  of  changes  which  balance  or  compensate  in 
some  way  the  progressive  changes,  and  these  are  the  changes  which 
lead  to  dedifferentiation  (see  following  section). 

Where  all  cells  or  parts  are  alike,  self -differentiation  must  pro- 
duce the  same  result  in  all,  but  where  differences  of  any  sort  exist, 
such,  for  example,  as  differences  in  metabolic  rate  between  external 
surface  and  interior  or  between  other  parts,  then  the  different  parts 
may  influence  each  other  and  differentiation  becomes  a  correlative 
process  which  may  result  in  the  production  of  many  different  parts. 
In  correlative  differentiation  the  parts  may  influence  each  other  in 
various  ways.  Dynamic  changes  of  one  kind  or  another  may  be 
transmitted  from  one  part  to  another;  quantitative  or  qualita- 
tive differences  in  the  chemical  substances  produced  by  different 


THE  LIFE  CYCLE  51 

parts  may  affect  the  course  of  metabolism  in  other  parts,  and 
differences  in  the  rate  of  growth  of  different  parts  may  produce 
mechanical  effects.  Since  the  action  of  external  factors  is  variable, 
both  in  time  and  in  space,  it  is  impossible  for  a  cell  or  cell-mass  to 
exist  for  any  considerable  length  of  time  under  natural  conditions 
without  local  differences  of  some  sort,  temporary  or  permanent, 
quantitative  or  quahtative,  appearing  in  it  in  consequence  of  the 
differential  action  of  external  factors. 

Dift'erentiation  of  some  degree  and  kind  is  then  a  necessar>-  and 
inevitable  result  of  continued  existence  except  where  the  progressive 
changes  are  balanced  or  compensated  in  some  way,  and  we  must 
distinguish  self -determining,  correlative,  and  external  factors  in 
the  process.  In  general,  as  I  have  pointed  out  above,  the  gradual 
accumulation  and  increase  in  physiological  stabihty  of  the  proto- 
plasm, either  through  change  in  chemical  constitution  or  aggregate 
condition  or  both,  is  self-determined  and  results  from  the  nature 
of  metabolism  and  the  constitution  of  protoplasm,  while  the  correl- 
ative and  external  factors  play  a  part  in  determining  the  character 
of  the  structural  substratum  thus  produced. 

The  process  of  differentiation  once  initiated,  each  step  becomes  a 
factor  bringing  about  further  changes.  For  example,  the  character 
of  the  substances  accumulated  in  a  cell  seems  to  depend  to  a  greater 
or  less  extent  upon  the  conditions  in  the  cell  which  affect  metabolic 
rate,  such  as  aggregate  condition  of  protoplasm,  enzyme  activity, 
etc.  In  embryonic,  undifferentiated  cells,  where  the  internal 
conditions  permit  a  high  metabolic  rate,  only  those  substances 
which  form  the  general  metabolic  substratum,  i.e.,  protoplasm, 
remain  as  constituents  of  the  cell,  but  as  the  self-determined  meta- 
boHc  rate  decreases,  other  substances  begin  to  appear  and  remain 
in  the  cell.  Undift'erentiated  protoplasm  is  protoplasm  reduced 
morphologically  to  its  lowest  terms.  Apparently  the  metabolic 
rate  in  the  cell,  or  the  internal  conditions  on  which  the  metabolic 
rate  depends,  are  factors  in  determining  the  physiological  stabilit\-  of 
substances.  Substances  which  are  either  not  formed  or  arc  broken 
down  and  eliminated  after  formation  in  cells  with  a  high  metabolic 
rate  appear  as  more  or  less  permanent  structural  components 
in   cells  with   a   lower   rate.     As   the   self-determined    metabolic 


52  SENESCENCE  AND  REJUVENESCENCE 

rate  decreases,  new  features  appear  as  relatively  stable  com- 
ponents of  the  structural  substratum,  and  these  become  factors  in 
further  changes.  Probably  also  substances  which  were  sufficiently 
stable  physiologically  to  become  components  of  the  structural  sub- 
stratum at  the  higher  metabohc  rate  become  more  stable  as  the 
metaboHc  rate  decreases,  not  necessarily  because  of  changes  in 
themselves,  but  because  of  the  decrease  in  rate,  or  the  conditions 
which  determine  it.  Thus  the  visible  substratum  of  the  cells 
becomes  more  and  more  altered  from  its  original  condition,  and 
apparently  the  farther  these  changes  go  the  less  the  abihty  of  the 
cell  to  synthesize  protoplasm — i.e.,  the  general  metaboHc  sub- 
stratum of  the  organism — and  the  less  "protoplasmic"  does  its 
structure  become. 

The  non-protoplasmic  substances  which  appear  in  the  cell, 
either  in  definite  morphological  form  or  as  granules,  droplets,  or 
inclosures  in  the  protoplasm,  have  very  commonly  been  grouped 
together  under  the  head  of  metaplasm.  Kassowitz  ('99),  for  ex- 
ample, makes  a  sharp  distinction  between  protoplasm  and  meta- 
plasm and  believes  that  only  the  accumulation  of  the  latter  is 
responsible  for  decrease  in  metaboHc  rate  in  the  cell.  The  distinc- 
tion is  doubtless  of  value  theoretically,  but  practically  it  is  impos- 
sible to  say  what  is  protoplasm  and  what  is  metaplasm.  And 
there  can  be  no  doubt  that  the  so-called  metaplasmic  substances 
often  take  more  or  less  part  in  the  metaboHc  activity  of  the 
ceU  instead  of  being  inactive,  as  Kassowitz  and  others  have 
maintained.  It  seems  therefore  more  in  accord  with  the  facts 
to  regard  the  cellular  substratum  as  showing  aU  gradations  from 
the  purely  protoplasmic  condition  of  the  embryonic  cell  to  the 
highly  differentiated  cell  which  may  be  loaded  with  substances 
obviously  non-protoplasmic  in  nature. 

Differentiation  is  very  generally,  though  not  necessarily,  as- 
sociated with  growth.  It  is  probable  that  growth  cannot  proceed 
very  far  without  bringing  about  some  degree  of  differentiation,  for 
the  accumulation  in  the  metaboHc  substratum  of  substance,  what- 
ever its  nature,  must  result  sooner  or  later  in  altering  metabolic 
conditions.  On  the  other  hand,  change  in  conditions  external  to  a 
cell  or  part  may  bring  about  differentiation  without  growth. 


THE  LIFE  CYCLE  53 

According  to  the  theory  of  differentiation  developed  here,  the 
self-determined  rate  of  metabolism  of  the  cell  must  be  to  some 
extent  an  index  of  its  degree  of  differentiation.  This  is  to  be  ex- 
pected, since  the  metabolic  rate  must  depend  upon  the  condition 
of  the  metabolic  substratum.  It  is  important  to  note  that  it  is 
the  metabohc  rate,  as  determined  by  conditions  existing  within 
the  cell  independently  of  external  stimulation,  which  is  thus  related 
to  the  degree  of  differentiation.  IMany  highly  differentiated  cells 
with  a  low,  self-determined  metabolic  rate  are  capable  temporarily 
of  a  very  high  rate  when  stimulated  from  external  sources.  Such 
increases  in  rate  are  evidently  the  result  of  changes  in  the  cellular 
substratum  which  are  largely  or  wholly  reversible.  What  their 
nature  is  we  do  not  know  certainly,  although  various  theories  of 
stimulation  have  been  advanced.  As  differentiation  proceeds 
beyond  a  certain  stage,  even  the  metabohc  rate  following  stimu- 
lation decreases  and  the  cell  becomes  less  and  less  capable  of  per- 
forming its  special  function  as  a  differentiated  cell. 

In  general,  a  greater  degree  of  differentiation  of  cells  is  one  of 
the  features  which  distinguish  the  so-called  higher  organisms  from 
the  lower.  A  comparison  of  the  cells  of  higher  and  lower  forms 
and  of  their  course  of  differentiation  seems  to  indicate  very  clearly 
that  the  physiological  stabihty  of  the  substratum  must  be  greater 
even  in  the  embryonic  cells  of  the  higher  than  in  those  of  the  lower 
forms  in  order  to  serv'^e  as  a  basis  for  the  more  rapid  and  greater 
differentiation  which  the  higher  forms  show.  Whether  the  rate  of 
metabolism  per  unit  of  weight  and  under  similar  conditions  of  tem- 
perature, etc.,  is  lower  in  the  higher  than  in  the  lower  forms  is  not 
at  present  known,  but  there  is  some  evidence  that  it  is.  If  increase 
in  physiological  stability  of  the  cellular  substratum  has  occurred 
during  the  course  of  evolution,  it  must  have  been  an  essential 
factor  in  determining  the  increase  in  structural  complexity  which 
is  so  characteristic  a  feature  of  evolution,  and  structural  evolution 
must  then  be  regarded  as  in  some  degree  an  equihbration  process, 
a  change  from  a  less  stable  to  a  more  stable  condition. 

The  orderly  sequence  of  the  process  of  organic  differentiation 
and  the  constancy  of  the  results  in  a  given  species  must  result  from 
certain   definite   characteristics   of    the   organic   individual.     My 


54  SENESCENCE  AND  REJUVENESCENCE 

own  experimental  investigations  have  forced  me  to  the  conclusion 
that  the  organic  individual  consists  of  a  dominant  and  of  sub- 
ordinate parts  and  that  dominance  and  subordination  in  their 
simplest  terms  depend  upon  rate  of  metabolism  (see  chap.  ix). 
Not  only  does  the  evidence  indicate  that  this  is  the  case,  but  it  is 
impossible  to  conceive  of  a  definite,  orderly  process  of  differentia- 
tion attaining  a  definite  constant  result  in  a  complex  physico- 
chemical  system  without  some  sort  of  dominance  and  subordination 
in  the  processes  involved.  In  a  complex  system  consisting  of  co- 
ordinate parts  the  process  of  differentiation  must  differ  widely  in 
character  according  to  conditions,  and  the  orderly  character  of 
development  and  constancy  of  result  which  we  find  in  organisms 
would  be  impossible. 

Most  theories  of  the  constitution  of  the  organism  have  failed  to 
recognize  the  necessity  for  such  a  relation  of  dominance  and  sub- 
ordination between  parts  as  a  fundamental  feature;  consequently 
they  have  failed  to  account  satisfactorily  for  the  orderly  course  and 
definite  result  of  differentiation.  Driesch  is  one  of  the  few  who 
have  seen  clearly  that  the  organic  individual  is  impossible  without 
a  controlhng  and  ordering  principle  of  some  sort,  and  not  finding 
any  physico-chemical  basis  for  such  a  principle,  he  has  vested  the 
control  in  entelechy.  As  regards  plants,  the  dominance  of  the 
vegetative  tip  over  other  parts  has  been  clearly  demonstrated, 
but  no  such  relation  of  parts  in  animal  development  has  been 
generally  recognized  by  zoologists.  Nevertheless  such  a  relation 
exists  and  must  exist,  for  without  it  development,  as  we  know  it, 
is  impossible. 

Dedifferentiation. — -Dedifferentiation  is  a  process  of  loss  of 
differentiation,  of  apparent  simplification,  of  return  or  approach  to 
the  embryonic  or  undifferentiated  condition.  Zoologists  have  been 
slow  to  admit  its  occurrence.  According  to  Weismann — and  many 
agree  with  him — development  proceeds  always  in  one  direction 
and  dedifferentiation  is  impossible.  Whenever  a  new  development 
of  a  part  or  a  whole  occurs,  it  originates  from  cells  or  parts  of  cells 
which  have  not  undergone  differentiation  beyond  the  stage  at  which 
the  new  development  begins.  Whenever  cells  which  are  visibly 
differentiated  give  rise  to  new  wholes  or  parts,  as  they  often  do  in 


THE  LIFE  CYCLE  55 

cases  of  regeneration,  it  is  assumed  that  they  contain  either  some 
of  the  undifferentiated  germ  plasm  or  those  elements  of  the  germ 
plasm  which  are  necessary  for  the  formation  of  the  new  part.  Such 
assumptions  are  not  only  unsatisfactory  because  they  cannot  be 
proved  or  disproved,  but  they  are  wholly  unnecessary.  We  have 
seen  that  the  organism  can  not  only  accumulate  structural  material 
of  various  kinds,  but  under  other  conditions  can  remove  to  a 
greater  or  less  extent  the  material  previously  accumulated.  Since 
reduction  occurs  in  organisms,  we  must  at  least  admit  the  possi- 
bility of  dedifferentiation.  Consideration  of  the  data  of  observ^a- 
tion  and  experiment  is  postponed  to  later  chapters:'  at  present 
only  certain  general  features  of  the  process  need  be  considered. 

In  the  case  of  self-differentiation  (see  pp.  50,  51)  the  gradual 
changes  in  the  substratum  may  be  reversed  in  direction  under 
altered  conditions;  the  gel  may  again  become  a  sol.  But  the 
synthesis  of  new  colloid  molecules  and  the  formation  of  new  sol, 
on  the  one  hand,  and  the  gradual  breakdown  and  elimination  of 
the  old  gel,  on  the  other,  is  also  possible.  Apparently  nuclear  and 
cell  division  are  or  may  be  factors  in  dedifferentiation.  With  the 
occurrence  of  division  the  progressive  changes  in  the  cell,  since  the 
preceding  division,  disappear  more  or  less  completely  and  the  cell 
returns  to  or  approaches  its  original  condition.  An  increase  in 
metabolic  rate  is  also  apparently  associated  with  division.^  If 
the  changes  in  one  direction  balance  those  in  the  other,  cells  which 
divide  may  remain  indefinitely  embr^'onic,  like  the  vegetative  tissues 
of  plants  and  the  growing  regions  of  certain  animals.  But  if  the 
nucleus  or  cell  does  not  divide,  or  if  division  does  not  bring  the 
cell  back  to  its  original  condition,  then  a  progressive  change  must 
occur  in  the  cell  or  from  one  cell  generation  to  another,  and  this 
change  appears  sooner  or  later  as  differentiation  and  may  go  so 
far  that  the  cell  finally  becomes  incapable  of  division.  Where 
differentiation  has  been  a  correlative  process,  isolation  of  a  part 
from  the  influence  of  the  correlative  factors  which  have  determined 
the  course  of  its  differentiation  may  result,  if  the  part  is  capable  of 
reacting  to  the  altered  conditions,  in  metabolic  changes  of  such  a 

'  See  particularly  chap,  v,  and  chap,  x,  pp.  245-47. 

'  See  chap,  vi,  pp.  141-42,  and  also  Lyon,  '02,  '04;  Spaulding,  '04;  Mathews,  '06. 


56  SENESCENCE  AND  REJUVENESCENCE 

character  that  substances  previously  accumulated  as  structural 
components  of  the  part  are  now  broken  down  and  eliminated,  and 
this  is  dedifferentiation. 

If  the  cell  is  a  physico-chemical  system  and  not  an  entity  sui 
generis,  the  occurrence  of  dedifferentiation  is  no  more  difficult  to 
account  for  than  the  reappearance  of  a  certain  kind  of  chemical 
reaction  in  a  non-Uving  chemical  system  when  conditions  which 
altered  the  character  of  the  reaction  have  ceased  to  act.  The 
occurrence  of  both  differentiation  and  dedifferentiation  is  exactly 
what  we  should  expect  from  the  physico-chemical  point  of  view. 
The  assumptions  of  the  germ-plasm  theory  merely  compUcate  and 
befog  the  whole  problem,  and  not  only  that,  but,  as  pointed  out  in 
the  preceding  chapter,  the  theory  is  essentially  "vitaUstic"  and 
even  pluralistic  in  its  logical  implications. 

Within  the  last  few  years,  however,  many  cases  of  dedifferen- 
tiation have  been  recorded  and  various  authors,  among  them 
LilUe,  Loeb,  Driesch,  Schultz,  and  others,  have  suggested  that 
development  in  animals  is  a  reversible  process.  But  reversibihty 
of  development,  so  called,  is  not  necessarily  reversibility  in  the 
chemical  sense.  Dedifferentiation  may  conceivably  result  from 
the  breakdown  and  eUmination  of  the  differentiated  substratum 
or  certain  components  of  it,  and  the  synthesis  of  new  undifferen- 
tiated substances  from  nutritive  material,  as  well  as  by  the  reversal 
of  the  reactions  which  occurred  in  the  differentiation.  As  in  the 
case  of  growth  and  reduction,  it  would  certainly  simpUfy  our  con- 
ception of  the  process  of  development  if  we  could  regard  it  as  a 
reversible  chemical  reaction,  but  such  a  conception  can  only  lead 
us  astray.  Undoubtedly  many  reversible  reactions  are  concerned 
in  development,  but  development  itseff  is  not  a  reversible  reaction. 
In  fact,  it  is  not  simply  a  chemical  reaction  of  any  kind,  but  an 
exceedingly  complex  series  of  interrelated  physical  and  chemical 
changes.  Reversal  of  development  may  result  from  relative 
changes  in  the  rate  of  certain  reaction  components  of  the  meta- 
bohc  complex  as  well  as  from  reversal  of  reaction.  In  fact,  it  is 
probable  that  reversal  of  development  occurs  at  least  as  frequently 
in  this  way  as  by  reversal  of  reaction.  A  change  in  metabolism, 
for  example,  such  that  a  substance  which  has  previously  been 


THE  LIFE  CYCLE  57 

accumulated  as  a  structural  component  of  the  cell  is  now  broken 
down,  oxidized,  and  eliminated,  may  bring  about  dedifferentiation, 
but  it  is  not  necessarily  a  reversal  of  reaction  in  the  chemical  sense, 
for  the  breakdown  and  ehmination  of  the  substance  may  be  a 
different  process  dependent  upon  different  factors  from  its  syn- 
thesis out  of  nutritive  substances. 

In  order  then  to  avoid  the  possibihty  of  confusion,  it  is  prefer- 
able to  regard  development,  not  as  reversible,  but  as  regressible. 
Differentiation  is  a  progression  from  one  condition  to  another, 
dedifferentiation  a  regression,  but  perhaps  through  stages  very 
different  from  the  stages  of  progression. 

Apparently  not  all  differentiated  cells  are  capable  of  dediffer- 
entiation to  the  embryonic  condition;  at  least  dedifferentiation 
fails  to  occur  in  many  cases  under  any  conditions  with  which  we 
are  familiar.  In  general,  less  highly  differentiated  cells  undergo 
dedifferentiation  more  readily  and  more  completely  than  more 
highly  differentiated;  consequently  dedifferentiation  is  much 
more  conspicuous  in  the  lower  than  in  the  higher  forms,  although 
even  in  man  some  cells  are  capable  of  more  or  less  dedifferentiation. 
This  limitation  of  dedifferentiation,  as  well  as  the  advance  of  differ- 
entiation, in  the  course  of  individual  development  and  evolution, 
suggests  again  an  increase  in  the  physiological  stabiHty  of  the 
cellular  substratum. 

Dedifferentiation  may  be  brought  about  in  cells  capable  of  it 
either  by  forcing  the  cell  to  use  up  its  own  substance  as  a  source 
of  energy  and  so  undergo  reduction,  as  in  starvation,  or  by  isolating 
the  cell  from  the  action  of  the  correlative  factors  which  have 
brought  about  differentiation,  and  in  some  cases,  and  to  a  certain 
degree,  simply  by  increasing  the  rate  of  metabohsm  of  the  cell  by 
stimulation  or  otherwise.  Reduction,  except  perhaps  in  embryonic 
cells,  is  probably  impossible  without  some  degree  of  dediiTerentia- 
tion,  but  dedifferentiation  may  occur  without  reduction.  Since  the 
differentiated  cell  has  in  general  a  low  rate  of  metabohsm  as  com- 
pared with  the  embryonic  cell,  and  since  the  decrease  in  rate  is 
associated  with  differentiation,  we  should  expect  that  an  increase 
in  rate  would  occur  during  dedifferentiation,  and  this,  as  will  appear, 
is  apparently  the  case. 


58  SENESCENCE  AND  REJUVENESCENCE 

If  the  suggestions  of  the  preceding  section  concerning  the  nature 
of  differentiation  are  correct,  we  should  expect  the  most  recently 
developed  morphological  features  of  the  cell  to  disappear  first  in 
dedifferentiation,  since  these  are,  under  the  conditions  existing  in 
the  cell,  the  least  stable  of  the  substratal  constituents.  As  these 
are  removed  the  rate  of  metaboHsm  rises  and  other  parts  of  the 
substratum  become  relatively  unstable  and  disappear,  and  so  on, 
until  the  cell  once  more  approaches  the  embryonic  condition.  So 
far  as  the  course  of  morphological  dedifferentiation  has  been  fol- 
lowed, it  seems  in  general  to  proceed  in  this  way  and  so  to  reverse  the 
course  of  differentiation.  But  this  does  not  necessarily  involve  a 
reversal  of  reaction  any  more  than  the  removal  of  a  previously 
deposited  sand-bar,  by  acceleration  or  change  of  course  of  the  cur- 
rent of  a  river,  involves  a  reversal  of  its  flow. 

The  dedifferentiating  cell  is  apparently  capable  at  any  stage 
of  resuming  the  process  of  differentiation,  and  if  dedifferentiation 
proceeds  far  enough  it  may,  under  altered  correlative  conditions, 
begin  a  new  course  of  differentiation  and  become  a  different  kind 
of  a  cell  from  that  which  it  was  originally.  As  the  sand-bar  formed 
in  the  stream  under  certain  conditions  may  under  others  be  re- 
moved and  its  place  taken  by  a  deep  channel,  and  again  the  channel 
may  give  place  to  a  mud  flat  or  a  beach,  so  the  original  morpho- 
logical differentiation  of  the  cell  may  disappear  and  give  place  to 
other  kinds  of  differentiation  as  the  physiological  conditions  change. 

THE  BASIS  or  SENESCENCE  AND  REJUVENESCENCE 

The  association  of  a  colloid  substratum  with  a  chemical  reaction- 
system  and  the  occurrence  of  growth  and  reduction  and  of  differ- 
entiation and  dedifferentiation  lead  us  to  a  conception  of  senescence 
and  rejuvenescence  which,  as  will  appear  in  following  chapters, 
seems  to  be  the  only  one  which  is  in  full  agreement  with  the  facts 
of  experiment  and  observation.  According  to  this  view,  senescence 
is  primarily  a  decrease  in  rate  of  dynamic  processes  conditioned  by 
the  accumulation,  differentiation,  and  other  associated  changes  of 
the  material  of  the  colloid  substratum.  Rejuvenescence  is  an 
increase  in  rate  of  dynamic  processes  conditioned  by  the  changes 
in  the  colloid  substratum  in  reduction  and  dedifferentiation. 


THE  LIFE  CYCLE  59 

Senescence  is  then  a  necessary  and  inevitable  feature  of  growth 
and  differentiation,  while  rejuvenescence  is  associated  with  reduc- 
tion and  with  the  various  reproductive  processes  in  which  more 
or  less  differentiated  parts  of  the  organism  undergo  dediffcrentia- 
tion.  Even  as  regards  gametic  or  sexual  reproduction,  the  facts 
indicate  that  the  gametes  or  sex  cells  are  very  highly  specialized 
and  differentiated  cells  and  that  early  embryonic  development  is 
essentially  a  period  of  dedifferentiation  and  rejuvenescence. 

Viewed  from  this  standpoint,  life  is  then  really  a  cychcal  pro- 
cess as  it  appears  to  be.  The  organism  grows,  differentiates,  and 
ages,  and  these  processes  lead,  usually  in  nature  through  reproduc- 
tion of  one  kind  or  another,  to  reduction,  dedifferentiation,  and 
rejuvenescence.  No  part  of  the  organism  remains  perpetually 
undifferentiated  and  perpetually  young.  The  young  organism 
arises  from  the  old,  not  from  a  self-perpetuating  source  of  youth, 
which  is  itself  always  young,  and  the  young  becomes  old  again. 

REFERENCES 

Babcock,  S.  M. 

191 2.     "Metabolic  Water:  Its  Production  and  Role  in  Vital  Phenomena," 
Univ.  of  Wisconsin  Agric.  Expt.  Sta.  Research  Bull.  No.  22. 

CmLD,  C.  M. 

1911.  "Experimental  Control  of  Morphogenesis  in  the  Regulation  of 
Planaria,"  Biol.  Bull.,  XX. 

Davenport,  C.  B. 

1897.     Experimental  Morphology.     New  York. 

Huxley,  T.  H. 

1853.     "Review  of  the  Cell  Theory,"  British  and  Foreign  Med.  Chir. 
Rev.,  XII. 

Kassowitz,  M. 

1899.     Allgemeine  Biologic.     Wien. 

Lepeschkin,  W.  W. 

191 2,  "Zur  Kenntnis  der  Einwirkung  suppramaximalcr  Tempcraturcn 
auf  die  Pflanze,"  Berichte  d.  deutsch.  hot.  Ges.,  XXX. 

Loeb,  J.,  and  Wasteneys,  H. 

191 1.     "Sind  die  Oxydationsvorgiinge  die  unabhangigc  Variable  in  den 
Lebenserscheinungen  ?"  Biochcm.  Zeitschr.,  XXX\'I. 


6o  SENESCENCE  AND  REJUVENESCENCE 

Lyon,  E.  P. 

1902.  "Effects  of  Potassium  Cyanide  and  of  Lack  of  Oxygen  upon  the 
Fertilized  Eggs  and  the  Embryos  of  the  Sea  Urchin  (Arbacia 
punctulata) ,"  Am.  Jour,  of  Physiol.,  VII. 

1904.  "Rhythms  of  Susceptibility  and  of  Carbon  Dioxide  Production 
in  Cleavage,"  Am.  Jour,  of  Physiol.,  XL 

Mathews,  A.  P. 

1906.  "A  Note  on  the  Susceptibility  of  Segmenting  Arbaciaa,nd  Asterias 
Eggs  to  Cyanides,"  Biol.  Bull.,  XL 

Pfeffer,  W. 

1901.     Pflanzenphysiologie,  Band  II.     Leipzig. 

SCHULTZ,  E. 

1904.  "Uber  Reduktionen:  I,  tJber  Hungererscheinungen  bei  Planaria 
lactea,"  Arch.  f.  Entwickelungsrnech.,  XVIII. 

Spaulding,  E.  G. 

1904.  "The  Rhythm  of  Immunity  and  Susceptibility  of  Fertilized  Sea 
Urchin  Eggs  to  Ether,  to  HCl  and  to  Some  Salts,"  Biol.  Bull,  VI. 


PART  II 

AN  EXPERIMENTAL  STUDY  OF  PHYSIOLOGICAL  SENESCENCE 
AND  REIUVENESCENCE  IN  THE  LOWER  ANI]\L\LS 


CHAPTER  III 

THE  PROBLEM  AND  METHODS  OF  INVESTIGATION 

THE  NATURE  OF  THE  PROBLEM 

Both  morphological  and  physiological  changes  are  involved  in 
the  processes  of  senescence  and  rejuvenescence,  and  we  may  attack 
the  problems  from  either  the  morphological  or  the  physiological 
side.  On  the  morphological  side  we  may  determine  the  changes 
in  physical  properties,  form,  and  structure  of  the  substratum  which 
occur  during  senescence  and  rejuvenescence,  and  on  the  ph}-sio- 
logical  side  we  may  investigate  the  changes  in  functional  activity 
and  in  metabolism. 

Concerning  the  morphological  changes  associated  with  senes- 
cence, particularly  in  the  higher  animals  and  man,  we  already 
possess  a  considerable  body  of  facts.     As  regards  the  physiological 
changes,  we  know  that  in  the  higher  animals  and  man  the  rate  of 
metabohsm  per  unit  of  substance  undergoes  in  general  a  decrease 
with  advancing  age  from  very  early  stages  onward,   and   that 
sooner  or  later  a  decrease  in  functional  activity  and  a  general 
deterioration  of  the  organism  occurs.     Our  knowledge  concerning 
the  lower  animals  is  less  complete.     We  are  familiar  with  the  general 
course  of  development  and  differentiation  in  most  forms,  but  the 
morphological  differences   between  young   and   old   adults   have 
received    comparatively    httle    attention.     Of    the    physiological 
aspect  of  senescence  in  the  lower  forms  we  have  httle  positive 
knowledge.     We  know  that  in  most  forms  growth  is  more  rapid 
in  earher  stages  and  that  in  many  plants  and  animals  the  length 
of  Hfe  under  the  usual  conditions  is  more  or  less  definite,  and  in 
some  forms  we  can  observe  a  decrease  in  functional  activity  with 
advancing  age.     On   the  other  hand,   some  organisms   live  and 
remain  active  for  an  indefinite  period  and  apparently  do  not  grow 
old.     Few  attempts  have  been  made,  however,  to  determine  by 
analytic  investigation  the  significance  of  these  various  facts  and  to 
find  a  common  basis  for  them. 

63 


64  SENESCENCE  AND  REJUVENESCENCE 

As  regards  rejuvenescence,  biologists  are  not  even  agreed  that 
it  is  of  general  occurrence.  The  behef  that  the  germ  plasm, 
which  is  assumed  not  to  grow  old,  except  as  it  gives  rise  to  a  soma, 
is  the  only  source  of  young  organisms  has  been  so  general  that  the 
possibihty  of  rejuvenescence  has  received  but  Httle  consideration. 
Maupas'  classical  investigations  upon  the  infusoria  (Maupas,  '88, 
'8q)  seemed  to  indicate  that  a  process  of  rejuvenescence  leading  to 
a  larger  size  of  individuals  and  a  higher  rate  of  division  resulted 
from  conjugation  in  these  forms,  but  the  recent  work  of  Jennings 
('13)  makes  it  evident  that  this  is  certainly  not  always  the  case. 
The  work  of  E.  Schultz  ('04,  '08)  and  others  on  reduction  and 
dedifferentiation  in  the  lower  forms,  the  suggestions  of  a  number 
of  others  that  development  is  "reversible,"  Minot's  view  (Minot, 
'08)  that  the  egg  before  fertilization  is  an  old  cell  and  undergoes 
rejuvenescence  during  the  early  stages  of  embryonic  development, 
and  the  well-known  fact  that  in  plants  differentiated  cells  may  lose 
their  differentiation  and  give  rise  to  new  plants — -these  are  the  chief 
data  and  conclusions  which  we  possess  concerning  rejuvenescence. 

The  various  facts  have  led  to  the  formulation  of  various  theories 
and  suggestions  as  to  the  nature  of  senescence,  but  these  are  mostly 
based  rather  upon  observational  than  experimental  evidence,  and 
some  of  them  take  account  only  of  man  and  the  higher  animals 
and  so  do  not  apply  to  organisms  in  general,  while  others  are 
more  or  less  speculative  in  character  and  cannot  readily  be  tested. 
There  is  at  present  no  generally  accepted  theory  of  senescence, 
and  as  for  rejuvenescence  it  can  scarcely  be  said  that  any  theory 
exists. 

The  real  problem  before  us  is  then  that  of  finding  a  general 
basis  for  these  phenomena  which  is  applicable  to  all  cases,  not 
merely  to  those  in  which  the  organism  manifestly  grows  old,  repro- 
duces, and  dies,  but  also  to  those  in  which,  instead  of  dying,  the 
whole  organism  breaks  up  or  divides  into  new  individuals,  which 
repeat  the  cycle  of  growth,  development,  and  reproduction,  and 
finally,  to  those  cases  in  which  the  whole  organism  or  parts  of  it 
appear  not  to  grow  old,  but  live  on  indefinitely. 

The  first  step  toward  accompUshing  this  is  to  find  some  means 
of  determining  whether  an  individual  organism  in  a  given  case  is 


THE  PR0BLE:M  and  IMETHODS  OF  IWESTIGATIOX        6? 


:> 


young  or  old,  not  merely  morphologically  but  physiologically.     We 
can  of  course  distinguish  embryonic,  lar\'al,  and  juvenile  forms  from 
adults  by  their  morphological  characters,  and  in  many  cases  bv 
their  physiological  characters  as  well,  but  it  is  not  always  easy  to 
distinguish  younger  and  older  individuals  of  the  same  general  stage 
of  the  Ufe  cycle.     In  the  higher  animals  certain  morphological 
changes  which  are  apparently  characteristic  of  senescence  have 
been  observed  in  some  cells,  but  the  morphological  features  of  the 
cells  of  different  organisms  are  so  different  and  the  visible  changes 
so  sKght  in  many  cases  that,  though  it  is  usually  possible  to  dis- 
tinguish embryonic  from  definitely  differentiated  cells,  it  is  very 
often  impossible  to  distinguish  old  and  young  individuals  of  the 
same  general  stage  by  the  morphological  characters  of  their  cells. 
Measurements  of  the  metabolism  or  of  the  rate  of  growth  in  man 
and  the  mammals  show  that  the  rates  of  both  per  unit  of  weight 
decrease  as  age  advances,  but  the  methods  employed  for  such  forms 
are  not  readily  apphcable  in  many  other  cases,  because  of  the  con- 
ditions of  existence,  the  small  size,  the  low  rate  of  metabolism, 
etc.     In  the  course  of  my  investigation  of  the  process  of  reproduc- 
tion in  the  lower  invertebrates  a  method  based  on  the  physiological 
resistance  or  susceptibiUty  of  the  animals  to  certain  conditions  has 
been  developed,  which  has  proved  to  be  of  great  value  in  distin- 
guishing physiologically  young  from  old  organisms  as  well  as  for 
various  other  purposes. 

SUSCEPTIBILITY  IN  RELATION  TO  RATE  OF  METABOLISM 

It  is  a  famihar  fact  that  the  susceptibility  or  physiological 
resistance  of  man  and  the  higher  animals  to  various  external  factors, 
and  particularly  to  those  which  depress,  changes  with  advancing 
age,  and  I  have  found  that  this  is  also  true  for  the  lower  animals,  as 
far  as  they  have  been  tested.  On  the  basis  of  this  relation  between 
susceptibihty  and  physiological  age,  it  has  been  possible  to  develop 
a  method  which  not  only  enables  us  to  distinguish  differences  in 
age,  but  aft'ords  a  means  of  comparing  in  a  general  way  the  rates 
of  the  metabolic  processes,  or  of  certain  fundamental  metabolic 
reactions  in  different  animals.  This  method,  which  may  be  called 
the  susceptibility,  physiological  resistance,  or  sur\-ival-time  method, 


66  SENESCENCE  AND  REJUVENESCENCE 

consists  essentially  in  determining  the  length  of  life  of  different 
individuals  or  lots  under  certain  standardized  conditions  which  kill 
by  making  impossible  in  one  way  or  another  the  continuation  of 
metabolism. 

The  substances  used  in  my  determinations  of  susceptibility 
include  the  cyanides,  and  ethyl  alcohol,  ethyl  ether,  chloroform, 
chloretone,  acetone-chloroform,  and  in  some  cases  various  other 
narcotics.  Carbon  dioxide  and  water  in  which  large  stocks  of  the 
species  under  examination  have  been  kept  and  which  therefore 
contain  soluble  products  of  metabolism  have  also  been  used  in  a 
few  cases  with  essentially  similar  results.  Certain  conditions,  such 
as  lack  of  oxygen,  low  temperature,  and  high  temperature,  act  in 
much  the  same  way,  at  least  in  certain  cases  and  when  properly 
controlled.  In  my  experiments  the  cyanides  have  proved  most 
convenient  and  satisfactory,  because  the  concentrations  required 
are  very  low  and  osmotic  and  other  complications  are  neghgible, 
and  because  in  the  lower  animals,  which  have  been  chiefly  used, 
irritability  and  movement  persist  to  some  extent  almost  to  the 
death  point,  while  in  alcohol,  ether,  and  other  narcotics  they  dis- 
appear earlier.  There  is  no  doubt  that  a  relation  exists  between 
the  general  metabolic  condition  of  organisms,  or  their  parts,  and 
their  susceptibility  to  a  very  large  number  of  substances  which  act 
as  poisons,  i.e.,  which  in  one  way  or  another  make  metabolism 
impossible,  and  that  differences  'n  susceptibihty  may  be  used  with 
certain  precautions  and  within  certain  Kmits  as  a  means  of  distin- 
guishing differences  in  metabolic  condition  and,  more  specifically, 
differences  in  metabohc  rate. 

Concerning  the  nature  of  the  action  of  poisons  such  as  hydro- 
cyanic acid,  the  cyanides,  and  the  great  group  of  substances  com- 
monly called  narcotics,  opinions  at  present  differ  widely.  As 
regards  the  cyanides,  it  has  been  very  generally  beheved  since 
Geppert's  experiments  that  they  decrease  or  inhibit  cell  respiration 
directly  or  indirectly.'     Recent  experiments  by  Vernon,  Warburg, 

'  Carlson,  '07;  Gasser  and  Loevenhart,  '14;  Geppert,  '89;  Grove  and  Loevenhart, 
*ii;  Kastle  and  Loevenhart,  '01;  Loeb  and  Wasteneys,  '13a,  '13^;  Mathews  and 
Walker,  '09;  Richards  and  Wallace,  '08;  Vernon,  '06,  '09,  '10;  Warburg,  'loc,  '14c. 
Further  references  will  be  found  in  these  papers. 


THE  PROBLEM  AND  METHODS  OF  INVESTIGATION        67 

and  Loeb  and  Wasteneys  have  demonstrated  that  oxygen  consump- 
tion is  greatly  decreased  in  animals  by  cyanides,  and  it  has  also 
been  shown  experimentally  that  the  cyanides  inhibit  oxidations 
and  the  action  of  oxidizing  enzymes  in  various  cases  outside  the 
organism.  To  the  hypothesis  that  the  cyanides  inhibit  oxidations 
in  the  organism  the  objection  has  been  made  that  they  affect,  not 
only  aerobic  or  oxybiotic,  but  anaerobic  animals  as  well,  although 
in  the  latter,  oxidations  requiring  atmospheric  oxygen  do  not  occur. 
In  answer  to  this,  it  has  been  pointed  out  that  even  in  anaerobic 
forms  oxidations  occur,  the  oxygen  being  derived  from  substances 
in  the  body  instead  of  from  the  atmosphere. 

The  cyanides  and  other  substances  containing  the  cyanogen 
radical,  CN,  are  in  general  extremely  powerful  poisons,  but  their 
action  resembles  in  certain  respects  that  of  the  substances  known 
as  narcotics  or  anesthetics. 

The  characteristic  physiological  effect  of  all  these  substances  is 
a  decrease  or  complete  loss  of  irritability,  which,  however,  is  com- 
pletely reversible  up  to  a  certain  Umit  and  so  may  be  followed  by 
complete  recovery.  But  the  narcotics  are  like  the  cyanides  poisons, 
and  if  they  act  in  sufficiently  high  concentration  or  for  a  sufficiently 
long  time  they  bring  about  changes  of  some  sort  which  are  not 
reversible  and  which  lead  to  death  by  retardation  and  final  cessa- 
tion of  metabolism.  Scientific  investigation  has  thus  far  chiefly 
concerned  itself  with  the  narcotic,  i.e.,  the  reversible,  rather  than 
with  the  poisonous,  irreversible,  effects  of  these  substances.  ]\Iany 
theories  of  narcosis'  have  been  advanced,  and  most  of  them  are 
still  in  the  field.  Brief  mention  must  be  made  of  the  more  impor- 
tant among  these  theories. 

Verworn  and  his  school  have  long  maintained  that  narcotics 
decrease  the  oxidation  processes  and  the  respiratory  activity  of  the 
protoplasm,  and  Verworn  has  recently  suggested  that  the  narcotics, 
either  by  adsorption  or  by  loose  chemical  combination,  render  the 

'  The  following  references  include  some  of  the  more  important  literature  bearing 
upon  the  different  theories  of  narcosis:  Alexander  and  Cserna,  '13;  Bernard,  '75; 
Dubois,  '94;  Hober,  '10;  Kisch,  '13;  R.  S.  Lillie,  '12a,  '12b,  '13a.  '13ft.  '14;  I-ocb 
and  Wasteneys,  '13(1,  '136;  A.  P.  Mathews,  '10,  '13;  H.  Meyer,  '99,  '01;  Overton, 
'01;  J.  Traube,  '04a,  '046,  '08,  '10,  '11,  '13,  etc.;  Verworn,  '03,  '12,  '13;  Warburg, 
'loa,  '10b,  'loc,  'iia, 'lib, '12a, '12b,  '13,  '14a,  '14b,  '14c;  Winterstcin,  '02,  '05,  '13,  '14. 


68  SENESCENCE  AND  REJUVENESCENCE 

oxygen  carriers  of  the  cell  incapable  of  activating  the  molecular 
oxygen,  and  that  the  cell  consequently  asphyxiates.  A.  P.  Mathews 
and  some  others  have  maintained  that  the  action  of  narcotics 
upon  the  oxidations  is  direct  and  chemical,  and  Mathews  has  re- 
cently suggested  that  the  residual  valences  of  narcotic  substances 
are  responsible  for  their  action.  In  this  connection  it  may  be  noted 
that  the  temperature  coefficient  of  the  susceptibility  of  Planaria 
to  potassium  cyanide  and  alcohol  is  of  the  same  order  of  magnitude 
as  the  usual  temperature  coefficient  of  chemical  reactions  (Child, 
'13a).  This  fact  indicates  that  the  susceptibility  increases  in  the 
same  ratio  as  the  rate  of  chemical  reaction  and  therefore  suggests 
that  the  cyanide  and  alcohol  act  directly  upon  the  metabolic  reac- 
tions or  some  of  them.  But  this  relation  between  the  temperature 
coefficients  of  susceptibility  and  the  rate  of  chemical  reaction  can- 
not be  made  the  basis  of  positive  conclusions  because  it  is  possibly 
nothing  more  than  a  coincidence,  or  it  may  result  from  a  complex 
of  factors  which  we  cannot  analyze. 

Within  the  last  few  years  various  investigators  have  recorded 
results  at  variance  with  the  Verworn  theory  of  narcosis.  Warburg 
found  that  certain  narcotics  produced  narcosis  without  decreasing 
the  oxygen  consumption  of  the  organism.  Later  Loeb  and  Waste- 
neys  reported  very  similar  results.  They  found  that  in  some  forms 
of  narcosis  the  decrease  in  oxygen  consumption  was  very  slight, 
while  in  others  it  was  much  greater.  With  the  cyanides  particu- 
larly, narcosis  occurs  only  when  oxygen  consumption  is  greatly 
reduced,  while  in  alcohol  narcosis  the  decrease  in  oxygen  consump- 
tion may  be  very  sUght.  Oxygen  consumption  is  decreased  in 
all  cases,  however,  if  sufficiently  high  concentrations  of  the  nar- 
cotic are  used.  Kisch  has  concluded  from  certain  experiments 
on  protozoa  that  while  narcosis  does  decrease  certain  oxidations  it 
does  not  affect  all.  Winterstein  has  also  found  that  in  alcohol 
narcosis  of  the  spinal  cord  of  the  frog  a  slight  increase  rather  than 
a  decrease  in  oxygen  consumption  may  occur  even  when  irritability 
is  completely  lost;  there  is,  however,  no  increase  in  oxygen  con- 
sumption with  stimulation. 

Assuming  that  these  results  are  correct  and  not  due  to  unrecog- 
nized technical  or  other  sources  of  error,  we  are  forced  to  conclude 


THE  PROBLEM  AND  METHODS  OF  INVESTIGATIOX        69 

with  these  authors  that  decrease  in  oxidation  is  an  incident  or  a 
result  of  narcosis  which  may  or  may  not  occur,  and  that  the  funda- 
mental feature  must  be  sought  in  some  other  change.  As  regards 
some  of  these  experiments,  however,  certain  possible  sources  of 
error  exist  and  further  investigation  may  alter  the  results.  At 
present  it  is  difficult  to  conceive  how  narcosis  can  occur  without 
decrease  in  oxidation. 

Arguing  from  the  observed  parallehsm  between  the  fat  solu- 
bihty  of  various  substances  and  their  narcotic  power,  Meyer  and 
Overton  advanced  the  theory  that  the  cell  membrane  consisted 
in  at  least  a  considerable  part  of  lipoid  or  fatty  substances  and 
that  the  action  of  the  narcotics  was  determined  by  their  solubiUty 
in  these  substances.  This  theory  has  undergone  development  and 
modification  at  the  hands  of  later  investigators,  and  the  question 
as  to  the  nature  of  the  narcotic  action  of  the  substances  which 
enter  the  cell  by  dissolving  in  the  Hpoids  of  the  membrane  has 
received  various  answers.  Some  have  held  that  the  hpoids  of  the 
membrane  were  responsible  only  for  the  entrance  of  the  narcotics, 
which  once  inside  the  cell  acted  chemically  or  otherwise.  Others 
believe  that  narcosis  is  the  result  of  the  changes  in  the  lipoids  of 
the  membrane  produced  by  the  narcotic  substances.  Warburg 
considers  the  physical  condition  of  the  lipoids  to  be  of  great  impor- 
tance in  connection  with  narcosis.  According  to  Hober,  narcosis 
occurs  when  the  narcotics  have  collected  to  a  certain  molecular 
concentration  in  the  cell  Hpoids,  because  the  narcotics  then  inhibit 
a  change  in  colloid  aggregate  condition  of  the  lipoids  which  is 
characteristic  of  excitation.  R.  S.  LiUie  finds  that  narcotics  de- 
crease the  permeabiUty  of  the  cell  membrane  or  its  ability  to 
undergo  increase  in  permeabihty,  and  so  decrease  or  inhibit  the 
increase  in  permeabihty  which  he  beheves  to  be  the  essential 
feature  of  stimulation. 

Some  forty  years  ago  Claude  Bernard  suggested  that  narcotics 
brought  about  a  partial  reversible  coagulation  of  the  protoplasm 
of  the  nerve  cell.  Later  Dubois  advanced  the  hypothesis  that  the 
narcotics  bring  about  loss  of  water  from  the  protoplasm  and  so 
decrease  metabolic  activity.  Recently  J.  Traube  has  concluded 
•on  the  basis  of  extensive  experimentation  that  the  narcotic  etlect 


yo  SENESCENXE  AND  REJUVENESCENCE 

is  due  to  changes  in  the  colloid  substratum.  According  to  Traube 
the  narcotics  act  by  decreasing  surface  tension  and  so  increasing 
the  degree  of  aggregation  of  the  cell  colloids,  and  decrease  in  oxida- 
tion or  in  metaboHsm  in  general  results  from  this  change  in  aggre- 
gate condition.  Other  factors  may  play  a  part  in  certain  cases, 
but  Traube  has  shown  that  a  relation  exists  in  many  cases  between 
the  decrease  in  the  surface  tension  of  water  by  narcotic  substances 
and  their  narcotic  power,  and  that  narcotic  concentrations  of 
many  different  substances  are  isocapillary,  i.e.,  decrease  surface 
tension  by  the  same  amount.  Warburg  has  shown  that  a  close 
interrelation  exists  between  the  oxidations  in  the  cell  and  the  funda- 
mental structure  and  that,  at  least  in  many  cases,  the  narcotics  de- 
crease oxidation.  He  concludes,  in  essential  agreement  with 
Traube,  that  the  narcotics  act  by  altering  surface  tension  and  so 
produce  capillary  changes,  particularly  in  the  lipoids. 

The  Kpoid  theory  of  Meyer  and  Overton  and  their  followers 
and  Traube's  surface  tension  theory  differ  from  Verworn's  asphyxi- 
ation theory  in  that  they  regard  the  decrease  in  metaboUc  activity 
in  narcosis  as  resulting  from  or  associated  with  the  changes  in  the 
colloid  substratum  of  the  cell.  The  unsatisfactory  character  of 
purely  or  pre-eminently  chemical  theories  of  the  organism  has 
been  pointed  out  in  chap,  i,  and  it  seems  probable  that  in  narcosis 
as  well  as  in  other  changes  in  chemical  activity  in  the  organism, 
the  substratum  and  the  changes  which  occur  in  it  must  be  taken 
into  account.  It  seems  not  improbable,  moreover,  that  narcosis 
is  not  always  produced  in  exactly  the  same  way.  Irritabihty,  as 
Winterstein  suggests,  probably  depends  upon  the  maintenance  of 
a  complex  dynamic  equihbrium  of  some  sort,  and  this  equilibrium 
may  be  destroyed  with  a  resulting  loss  of  irritabihty,  by  changes  of 
various  kinds  in  the  cell.  It  is  even  conceivable  that  in  some  cases 
the  change  may  concern  primarily  or  chiefly  the  substratum,  and 
in  other  cases  the  chemical  reactions,  or  certain  of  them,  and  we 
must  admit  the  further  possibihty  that  both  the  substratal  and  the 
chemical  changes  may  differ  with  different  narcotic  substances 
and  yet  produce  much  the  same  general  result  as  regards  irrita- 
bility. Various  observations  show  that  very  considerable  differ- 
ences do  exist  in  dift'erent  forms  of  narcosis.     It  was  noted  above 


THE  PROBLEM  AND  METHODS  OF  IWESTIGATIOX        71 

that  the  decrease  in  ox^^gen  consumption  may  apparently  difTer 
widely  in  different  narcoses,  and  Alexander  and  Cserna  have  found 
that  not  only  is  this  true,  but  that  the  decrease  in  carbon-dioxide 
production  is  not  parallel  to  the  decrease  in  oxidation  in  different 
brain  narcoses.  In  short,  it  is  possible  that  the  changes  in  the  cell 
which  bring  about  narcosis  may  differ  in  character  with  different 
narcotics  and  perhaps  with  different  cellular  conditions.  Perhaps, 
as  so  often  in  the  history  of  biological  theory,  all  the  theories  of 
narcosis  are  more  or  less  correct. 

But,  however  the  narcotic  substances  act  upon  the  cell,  there 
can  be  no  doubt  that  within  a  given  species  or  organism  a  general 
relation  exists  between  metabolic  condition  and  susceptibiUty  to  a 
given  narcotic.  Differences  in  metaboHc  condition  do  not  exist 
independently  of  differences  in  condition  of  the  colloid  substratum, 
and  whether  the  narcotic  aft'ects  primarily  the  substratum  or  cer- 
tain of  the  chemical  reactions,  the  susceptibility  of  the  organism 
or  part  to  its  action  must  differ  as  the  conditions  which  determine 
or  are  associated  with  metabohc  activity  differ. 

Narcosis  is  only  one  stage  in  the  action  of  the  narcotic  sub- 
stances. When  they  are  present  in  sufficiently  high  concentration 
or  act  for  a  sufficiently  long  time,  they  bring  about  changes  which 
are  not  reversible  and  which  finally  end  in  death  by  making  the 
continuation  of  metabohsm  impossible.  The  wide  range  of  varia- 
tion observed  in  some  cases  between  narcotic  and  killing  concen- 
trations, both  with  different  narcotics  and  with  the  same  narcotic 
at  diff'erent  stages  of  development  (Vernon,  '13),  indicates  that 
the  reversible  changes  involved  in  pure  narcosis  are  different  in 
some  way  from  those  which  result  in  death.  With  the  killing  con- 
centrations the  relation  between  susceptibility  and  metaboHc  con- 
dition is  more  distinct  and  uniform  than  with  the  lower,  purely 
narcotic  concentrations,  where  incidental  factors  may  sometimes 
mask  or  reverse  the  fundamental  relation  (see  pp.  75-76).  With 
the  cyanides,  however,  where  narcotic  and  killing  concentrations 
do  not  differ  very  greatly,  this  relation  appears  more  distinctly 
and  uniformly  than  with  any  other  agents  thus  far  used. 

It  cannot  of  course  be  maintained  that  the  susceptibility  to 
cyanides  or  other  narcotics  of  an  organism  or  part  at  a  given  moment 


72  SENESCENCE  AND  REJUVENESCENCE 

is  an  exact  measure  of  its  total  metabolism  at  that  moment.  If  the 
cyanides  or  other  narcotics  act  directly  on  the  oxidation  processes, 
a  general  relation  between  susceptibility  and  oxidation  must  exist, 
but  while  the  oxidations  are  fundamental  metabolic  reactions,  and 
serve  in  a  general  way  as  a  measure  of  metabolic  activity,  a  con- 
siderable range  of  variation  in  the  different  reactions  which  go  to 
make  up  the  the  metaboHc  complex  may  undoubtedly  exist.  If,  on 
the  other  hand,  these  substances  act  on  the  substratum  and  affect 
the  metaboUc  reactions  only  or  primarily  through  the  substratal 
changes,  susceptibility  must  be  related  to  the  general  average  of 
metaboKc  activity,  but  certain  reactions  may  be  more  affected  than 
others  in  the  early  stages  of  action,  though  sooner  or  later  the 
metaboHc  process  as  a  whole  is  retarded  or  inhibited. 

In  concentrations  of  the  cyanides  or  other  narcotics,  which  not 
only  narcotize  but  gradually  kill,  a  decrease  in  metabolism,  as 
measured  by  oxygen  consumption,  by  carbon-dioxide  production, 
by  functional  activity,  or  by  other  means,  occurs  in  all  cases,  and 
metaboHsm  finally  ceases.  In  concentrations  in  which  death 
occurs  at  times  varying  from  a  few  minutes  to  a  few  hours  and  when 
comphcating  factors  are  absent,  the  susceptibility  varies  directly 
with  the  general  metaboHc  rate.  Conditions  which  increase  meta- 
bolic activity  increase  susceptibility,  and  vice  versa.  This  method 
of  determining  susceptibiHty  I  have  called  the  direct  susceptibiHty 
method  (Child,  '13a). 

The  capacity  of  organisms  to  accHmate  themselves  to,  or  acquire 
a  tolerance  to,  narcotics  has  long  been  recognized:  this  capacity  is 
well  illustrated  by  the  high  degree  of  tolerance  for  alcohol,  cocaine, 
etc.,  developed  in  the  human  organism.  In  concentrations  of  nar- 
cotics which  are  sufficiently  low  to  permit  partial,  but  not  complete, 
accHmation,  we  find  that  the  relation  between  susceptibiHty  and 
metaboHc  rate  undergoes  reversal.  In  such  concentrations  the 
individual  or  part  with  the  higher  metaboHc  rate  becomes  more 
readily  and  more  completely  acclimated  and  therefore  Hves  longer 
than  the  individual  or  part  with  the  lower  metaboHc  rate  which  is 
unable  to  acclimate  itself  and  so  dies  earHer.  This  relation  between 
metaboHc  rate  and  capacity  for  acclimation  is  to  be  expected,  for 
the  occurrence  of  accHmation  evidently  depends  on  conditions  in 


THE  PROBLEM  AND  METHODS  OF  INVESTIGATION         73 

the  organism  which  are  associated  with  metaboUc  activity.  Thus 
the  metabohc  condition  of  different  individuals  or  parts  may  also  be 
compared  by  means  of  this  indirect  or  acclimation  method. 

These  diflferences  in  susceptibilit}-  to  narcotics,  particularly 
those  determined  directly  with  relatively  high  concentrations, 
afford,  when  properly  controlled,  a  very  dehcate  method  for  com- 
paring general  metabohc  rates  in  different  individuals  and  parts, 
at  least  in  many  of  the  lower  animals.  In  a  recent  paper  (Child, 
'13a)  the  technique  of  the  method  for  flatworms  and  similar  forms, 
its  different  modifications  and  its  hmitations  have  been  considered 
at  length.  As  regards  the  relation  between  susceptibihty  or  resist- 
ance to  cyanide  and  rate  of  metaboUsm,  it  was  shown  in  that 
paper  that  susceptibility  is  altered  by  motor  activity,  that  the 
temperature  coefficient  of  susceptibihty  is  of  the  same  order  of 
magnitude  as  that  of  most  chemical  reactions,  and  that  differences 
in  carbon-dioxide  production  correspond  to  differences  in  suscepti- 
bihty. 

The  estimations  of  carbon-dioxide  production  were  made  by  Dr. 
S.  Tashiro  with  the  "biometer"  devised  and  recently  described  by 
him  (Tashiro,  '13&).  The  sensitiveness  and  great  value  of  this 
apparatus  are  shown  by  the  fact  that  Tashiro  has  been  able  to 
demonstrate  the  production  of  carbon  dioxide  in  the  resting  nerve, 
its  increase  by  stimulation,  and  its  decrease  by  narcotics,  and  has 
also  shown  that  Hving  seeds  resemble  the  nerve  in  most  respects  as 
regards  irritability  (Tashiro,  '13a).  In  the  comparison  between  the 
results  of  the  susceptibihty  method  and  the  carbon-dioxide  produc- 
tion the  flatworm  Planaria  dorotocephala  (see  Fig.  6,  p.  93)  was 
used  in  most  cases.  The  susceptibihty  method  shows  that  the  rate 
of  metabolism  is  higher  in  young  than  in  old  animals,  in  star\'ed 
than  in  fed,  and  in  animals  stimulated  to  movement  than  in  resting 
animals.  In  distilled  water  the  rate  of  metabohsm  as  measured  by 
the  susceptibility  method  is  higher  and  in  5  per  cent  sea-water  lower 
than  in  tap-water.  In  pieces  isolated  by  cutting,  the  rate  of  metab- 
ohsm is  higher  in  long  anterior  pieces  than  in  posterior  pieces  of 
the  same  length  (cf.  Child,  '146).  In  each  of  these  cases  the  animal 
or  piece  which  possessed  the  higher  rate  of  metabolism  according 
to  the  susceptibility  method  produced  more  carbon  dioxide  than 


74  SENESCENCE  AND  REJUVENESCENCE 

the  other.  The  complete  agreement  between  the  two  methods 
indicates  very  clearly  that  both  are  concerned  in  one  way  or  another 
with  fundamental  metabohc  reactions  and  that  both  afford  a  very 
delicate  means  of  comparing  in  a  general  way  the  rates  of  these 
reactions. 

It  is  evident  that  accuracy  in  the  use  of  susceptibility  as  a 
method  of  investigation  depends  to  a  considerable  extent  upon 
the  exactness  with  which  it  is  possible  to  determine  the  quantitative 
effect  of  the  cyanide  or  other  agent  used  upon  the  organism.  In 
the  lower  invertebrates,  particularly  the  protozoa,  coelenterates, 
and  flatworms,  which  have  formed  the  material  for  most  of  my 
experiments,  and  in  the  early  stages  of  development  of  many  other 
animals  where  hard  skeletal  structures  are  absent  and  supporting 
tissues  do  not  possess  a  high  degree  of  firmness  and  coherence,  or 
are  entirely  absent,  death  is  followed  in  a  short  time,  often  at  once, 
by  more  or  less  complete  disintegration.  The  body  loses  its  form, 
swells,  breaks  down  into  a  shapeless  mass,  and  may  finally  dis- 
appear completely,  except  for  a  slight  turbidity  in  the  water,  which 
results  from  the  minute  particles  in  suspension.  In  such  cases, 
however,  movement  may  continue  to  some  extent,  particularly  in  the 
cyanides,  until  a  short  time  before  disintegration  begins,  or  in  some 
forms  up  to  the  very  instant  of  disintegration.  In  these  forms  then 
it  is  possible  to  determine  with  considerable  exactness  the  time  when 
death  occurs  and  so  to  compare  the  length  of  life  of  different  indi- 
viduals under  certain  specific  conditions,  e.g.,  a  certain  concen- 
tration of  cyanide,  alcohol,  etc.,  or  under  low  temperature  or  lack 
of  oxygen.  In  many  of  my  experiments  changes  of  this  kind  have 
been  taken  as  the  criterion  of  death,  but  essentially  the  same  results 
are  obtained  with  the  lower  animals  if  the  times  of  complete  cessa- 
tion of  movement  in  response  to  stimulation  are  determined  instead 
of  the  times  of  disintegration. 

Where  such  disintegration  does  not  occur,  or  is  retarded  by  the 
physical  consistency  of  the  organism  or  part  concerned,  it  is  often 
possible  to  determine  the  occurrence  of  death  in  small  animals  under 
the  microscope  by  other  changes  in  appearance,  such  as  an  increase 
in  opacity,  a  change  in  color,  etc.  Moreover,  all  these  methods  of 
determining  the  death  point  can  be  checked  and  the  time  of  death 


THE  PROBLEM  AND  METHODS  OF  INVESTIGATION         75 

determined  in  cases  where  such  methods  are  not  available  by 
determining  the  hmits  of  recovery,  i.e.,  at  stated  intervals  a  certain 
number  of  the  organisms  are  removed  from  the  narcotic  solution  to 
water:  the  length  of  time  in  the  narcotic  at  which  recovery  ceases 
to  occur  is  at  least  approximately  the  survival  time. 

With  the  flatworms  and  other  simple  naked  forms  the  suscepti- 
bility method  can  usually  be  employed  independently  of  dilTerences 
in  size,  for  in  such  cases  the  death  changes  at  the  surface  of  the  body 
may  be  used  as  a  basis  for  comparison.  Moreover,  in  such  elon- 
gated flattened  forms  as  the  flatworms,  surface  increases  almost 
as  rapidly  as  volume.  But  in  forms  where  the  permeable  surfaces 
are  Hmited  to  certain  regions  of  the  body  or  are  internal,  as  in  air- 
breathing  forms,  or  where  the  body  is  covered  by  an  exoskeleton, 
the  certain  elimination  of  the  factor  of  size  often  presents  a  difficult 
problem. 

While  most  of  my  determinations  of  susceptibility  have  been 
made  upon  the  lower  invertebrates,  some  experiments  with  the 
higher  invertebrates  and  the  lower  vertebrates  have  demonstrated 
that  the  relation  between  susceptibility  to  cyanide  and  general 
metabohc  rate  is  the  same  in  these  as  in  the  lower  forms.  But  at 
least  as  regards  the  vertebrates  this  is  not  true  for  all  narcotics. 
Vernon  ('13)  has  found,  for  example,  that  the  susceptibility  of  tad- 
poles to  some  narcotics  increases  and  to  others  decreases  with  ad- 
vancing age,  and  suggests  that  these  differences  are  due  to  changes 
in  the  constitution  of  the  cell  hpoids.  This  is  probably  not  the  only 
factor  concerned:  differences  in  the  lipoid  solubility  of  the  different 
narcotics  and  differences  in  the  amount  as  well  as  the  constitution 
of  lipoids  in  the  nervous  system  and  still  other  factors  are  probably 
also  involved,  but  further  investigation  is  necessary  before  the  sub- 
ject is  cleared  up.  In  the  lower  invertebrates  I  have  as  yet  found 
no  indication  of  such  differences  in  the  action  of  different  narcotics 
as  Vernon  describes.  With  some  narcotics  the  age  changes  in  sus- 
ceptibility are  greater  than  with  others,  but  in  all  cases  thus  far 
the  changes  during  a  given  developmental  period,  as  determined  by 
different  narcotics,  proceed  in  the  same  direction.  It  seems  prob- 
able that  the  differences  in  the  direction  of  change  in  susceptibility 
observed  by  Vernon  result,  at  least  in  part,  from  differences  in  the 


76  SENESCENCE  AND  REJUVENESCENCE 

relation  between  the  narcotics  and  the  cell  lipoids.     In  the  verte- 
brates the  accumulation  and  differentiation  of  lipoids,  particularly 
in  the  nervous  system,  is  very  much  greater  than  in  the  lower  inver- 
tebrates, and  it  is  probable  that  with  some  narcotics  which  are 
highly  fat  soluble,  the  fundamental  relation  between  susceptibility 
and  general  metabolic  condition  is  completely  masked,  or  even 
reversed,  by  their  higher  concentration  in  the  cells  of  the  nervous 
system  with  a  given  external  concentration,  and  consequently  by 
their  greater  narcotic  effect  on  these  cells.     In  the  lower  animals 
and  in  early  stages  of  development  the  action  of  narcotics  is  general, 
but  with  the  advance  in  differentiation  the  susceptibility  of  the 
nervous  system  as   compared  with  other  organs  increases  very 
greatly.     In  general  it  appears  that  the  differences  in  susceptibility 
to  all  narcotics  are  much  more  nearly  alike  in  the  lower  forms  and 
the  early  stages  of  all,  while  in  the  later  stages  of  the  higher  forms 
those  substances  which  are  highly  water  soluble  act  in  much  the 
same  way  as  in  the  lower  forms,  but  the  action  of  the  highly  fat- 
soluble  narcotics  is  modified  because  of  the  increasing  development 
and  differentiation  of   lipoids  in  the  nervous  system,  and  very 
probably  other  modifications  also   occur.     Nevertheless,   and  in 
spite  of  these  complicating  factors  which  appear  in  certain  cases, 
differences  in  susceptibility  to  various  agents  can,  with  proper 
precautions  and  checks,  be  used  to  a  certain  extent  as  a  means  of 
comparing  general  metabolic  condition,  even  in  the  vertebrates. 
The  use  of  the  cyanides  seems  to  be  freer  from  complicating  fac- 
tors than  that  of  other  agents. 

Undoubtedly,  however,  the  chief  value  of  the  susceptibility 
method  lies  in  its  applicability  to  small  simple  organisms  and  to 
different  regions  of  a  single,  intact,  not  too  highly  differentiated 
individual.  By  means  of  it  we  are  able  to  gain  some  idea  of  differ- 
ences in  metabolic  rate  in  many  cases  to  which  other  methods  are 
not  applicable. 

Thus  far  susceptibihty  to  narcotics,  cyanides,  and  other  sub- 
stances in  its  relation  to  metabolism  has  received  but  little  atten- 
tion. Lyon  ('02,  '04)  and  A.  P.  Mathews  ('06)  have  used 
susceptibility  to  cyanides  and  to  various  other  substances  and  con- 
ditions as  a  method  for  showing  differences  in  rate  of  metabolism 


THE  PROBLEM  AND  METHODS  OF  INVESTIG A TIOX         77 

in  the  cleavage  stages  of  eggs,  and  Loeb'  and  others  have  made  use 
of  the  cyanides  to  decrease  or  inhibit  the  oxidation  processes  in 
eggs,  and  Drzewina  and  Bohn  ('13)  have  observed  parallel  dilTer- 
ences  in  susceptibility  to  cyanides  and  lack  of  oxygen  along  the  lon- 
gitudinal body-axis  of  certain  flatworms.  Some  other  incidental 
observations  also  exist,  but  the  general  significance  of  dilTerences 
in  susceptibiHty  has  been  either  ignored  or  not  recognized. 

THE  DIRECT  METHOD 

By  this  method  the  resistance  or  susceptibility  is  determined 
directly  by  concentrations  of  cyanide  or  other  agents  which  kill 
the  animals  within  a  few  hours.  For  a  particular  species  a  con- 
centration must  be  determined  which  kills  without  acclimation, 
but  which  does  not  kill  so  rapidly  that  the  differences  in  suscepti- 
bility do  not  appear  clearly.  For  Planaria  dorotocephala  (see  p.  93) 
and  other  related  species  a  concentration  of  one  one-thousandth 
gram-molecular  solution  (o.ooi  mol.,  65  milligrams  per  Hter, 
0.0065  per  cent)  of  potassium  cyanide  has  been  found  most  satis- 
factory at  temperatures  about  20°  C.  and  for  most  purposes.  This 
kills  the  animals  in  from  two  to  twelve  hours  according  to  their  con- 
dition. But  a  range  of  concentrations  from  0.0002  mol.  up  to 
0.005  mol.,  or  even  higher,  may  be  used,  except  where  the  meta- 
bolic rate  is  very  high,  as  in  young  animals,  without  altering  any- 
thing but  the  time  factor.  Essentially  the  same  results  are  obtained 
from  4  per  cent  alcohol  or  from  2  per  cent  ether  as  from  o.ooi  mol. 
potassium  cyanide. 

Since  the  death  and  disintegration  of  different  parts  of  the  body 
usually  follow  a  regular  sequence  (Child,  '136),  it  is  possible  to 
determine  the  time,  not  merely  of  disintegration  of  the  whole  ani- 
mal, but  of  the  various  regions  of  the  body.  The  body  of  Planaria 
consists  of  two  or  more  zooids  (see  p.  123)  of  which  only  the  anterior 
one  is  morphologically  developed.  In  this  anterior  zooid  death  and 
disintegration  usually  begin  at  the  head-region  and  proceed  pos- 
teriorly, and  the  lateral  margins  of  the  body  usually  die  and  disin- 
tegrate before  the  median  region.     The  most  satisfactory  method 

'  Loeb,  '09,  '10;  Locb  and  Lewis,  '02;  Loeb  and  Wastenej's,  '10;  and  various 
other  papers. 


78  SENESCENCE  AND  REJUVENESCENCE 

of  recording  the  course  of  death  and  disintegration  has  proved  to 
be  that  of  examining  the  lots  of  animals  at  stated  intervals,  e.g., 
every  half-hour,  and  recording  the  condition  of  each  individual. 
In  order  to  accomplish  this  most  readily  five  stages  of  disintegra- 
tion have  been  more  or  less  arbitrarily  distinguished  as  follows: 

Stage  I.  Intact,  not  showing  any  appreciable  disintegration. 
Such  animals  or  pieces  are  always  alive  and  show  movement. 

Stage  II.  In  whole  animals  from  the  first  appearance  of  disin- 
tegration, which  is  practically  always  in  the  head-region,  to  the 
first  appearance  of  disintegration  of  the  lateral  margins  of  the  body. 
In  pieces,  from  the  beginning  of  disintegration  at  one  or  both  ends 
to  the  first  appearance  of  disintegration  on  the  lateral  margins. 
Considerable  motor  activity  may  still  be  present. 

Stage  III.'  In  both  whole  animals  and  pieces  from  the  appear- 
ance of  disintegration  on  the  lateral  margins  until  it  has  extended 
over  the  whole  length  of  the  margins.  Movement  may  still  occur 
in  the  parts  least  affected. 

Stage  IV.  From  the  end  of  Stage  III  to  the  time  when  the  sur- 
face of  the  body  in  the  median  regions  disintegrates.  iMotor 
activity  ceases. 

Stage  V.  Disintegration  has  extended  to  all  parts  of  the  sur- 
face and  the  progress  of  death  over  the  body  is  completed.  The 
remaining  parts  representing  the  internal  organs  gradually  swell 
and  break  up,  but  the  process  is  not  followed  beyond  the  completion 
of  surface  changes. 

Attention  must  be  called  to  the  fact  that  these  stages  represent 
primarily  the  progress  of  the  surface  changes  over  the  body  from 
one  region  to  another  rather  than  the  progress  of  disintegration 
through  the  internal  organs.  In  these  and  other  naked  animals 
differences  in  size  of  the  animal  do  not  aft'ect  the  progress  of  the 
surface  changes,  while  they  may  be  an  important  factor  in  the  rate 
of  penetration  of  the  reagent  and  consequently  in  the  disintegra- 
tion of  the  internal  organs.  But  since  the  surface  changes  in  any 
region  are  practically  coincident  with  the  death  of  that  region,  it  is 
not  necessary  to  follow  the  internal  changes,  and  in  naked-bodied 
animals  the  method  becomes  for  all  practical  purposes  independent 
of  size. 


THE  PROBLEM  AND  METHODS  OF  LWESTIGATION        79 

There  is  no  difficulty  in  distinguishing  between  these  five  stages 
with  sufficient  exactness  for  all  purposes.  Where  the  dilTerences 
in  rate  of  metabolism  between  two  animals  or  lots  are  great,  they 
are  clearly  shown  by  the  times  of  the  beginning  and  completion  of 
disintegration  in  each  lot,  but  by  following  the  dilTerent  stages  of 
the  process  it  is  possible  to  distinguish  slight  differences.  As  re- 
gards length  of  time,  the  different  stages  are  not  strictly  comparable 
in  all  cases;  in  large  animals,  for  example,  Stage  III  extends  over 
a  somewhat  longer  time  than  the  other  stages,  because  the  progress 
of  disintegration  along  the  margins  in  the  posterior  direction 
requires  a  longer  time  than  in  small  animals  and  pieces  where  the 
length  of  the  margins  is  much  less. 

In  comparing  susceptibilities  determined  at  different  times 
with  different  solutions,  great  care  is  necessary,  for  slight  differ- 
ences in  alkahnity  of  the  water  alter  the  susceptibility  very  con- 
siderably, and  susceptibihty  also  varies  with  the  temperature.  In 
order  to  avoid  these  and  other  compHcations,  whenever  possible 
susceptibilities  to  be  compared  should  be  determined  at  the  same 
time,  with  the  same  solution,  and  under  the  same  conditions  of 
temperature  and  light,  etc. 

Table  I  will  serve  as  an  example  of  the  method  of  recording  the 
observations  and  of  the  results  obtained.     In  this  table,  the  first 

TABLE  I 


Length  of  Time 
in  KCN 


0-30 1 

1 .  00 / 

\ 

I-30 1 

2 .  00 / 

2-3° I 

300 

3-3° 

4 .  00 

430 

S-oo 

S-30 


Lots 


6 
10 

2 
9 

8 
3 


Stages  of  Disintegration 


II 


7 
S 


III 


4 

2 


2 
10 

7 
I 


IV 


3 
6 

5 
3 


5 

9 

10 


3 

5 

7 

10 


8o 


SENESCENCE  AND  REJUVENESCENCE 


vertical  column  gives  in  hours  and  minutes  the  length  of  time  in 
cyanide  at  each  examination;  the  second  gives  the  serial  number 
of  each  lot,  and  the  five  columns  headed  by  Roman  numerals  under 
''Stages"  give  the  number  of  animals  of  each  lot  in  each  stage  of 
disintegration  at  each  examination.  In  this  case  Lot  i  consists 
of  ten  young  worms,  four  to  five  millimeters  in  length,  and  Lot  2 

Stages  and 
their  values 


Hours  o     ^ 


Fig.  3. — Planar ia  dorotocephala:  susceptibility  curves  of  young  (06)  and  old 
(cd)  animals  in  KCN  o.ooi  mol.  Graphic  presentation  of  the  data  of  Table  I.  The 
vertical  inter\'als  represent  the  arbitrary  numerical  values  of  the  average  disintegra- 
tion stages,  the  horizontal  intervals  half-hour  periods. 

of  ten  old  worms  fifteen  to  sixteen  millimeters  in  length,  both  from 
the  same  stock. 

The  table  shows  that  in  the  young  worms  of  Lot  i  disintegration 
begins  earlier  and  proceeds  more  rapidly  than  in  the  old  worms  of 
Lot  2.  The  young  worms  have  all  reached  Stage  V  after  two  and 
one-half  hours  in  cyanide,  while  none  of  the  old  worms  have  reached 
this  stage  at  this  time  and  all  of  them  reach  it  only  after  five  and 


THE  PROBLEM  AND  IVIETHODS  OF  INVESTIGATION        8i 

one-half  hours.  Essentially  the  same  differences  appear  in  4  per 
cent  alcohol,  in  2  per  cent  ether,  and  in  solutions  of  various  other 
depressing  agents. 

These  data  may  be  presented  more  clearly  and  briefly  in  graphic 
form,  as  in  Fig.  3,  which  is  a  graphic  presentation  of  Table  I.  In 
Fig.  3  the  curve  ab  is  the  death  curve  or  susccptibihty  curve  of  the 
ten  young  worms  of  Lot  i,  the  curve  cd  the  susceptibility  curve 
of  the  ten  old  worms  of  Lot  2.^  Each  curve  is  a  descending  curve: 
the  distance  of  its  starting-point  (a,  c,  Fig.  3)  to  the  right  of  the 
vertical  line,  the  axis  of  ordinates,  indicates  the  length  of  time 
between  placing  the  animals  in  cyanide  and  the  beginning  of  death 
and  disintegration;  its  slope  indicates  the  average  rate  of  disinte- 
gration; the  distance  of  its  lower  end  {b,  d,  Fig.  3)  from  the  axis 
of  ordinates  indicates  the  length  of  time  between  placing  the  animals 

'  The  transformation  of  the  tabulated  data  into  graphic  form  is  accomplished 
by  giving  a  numerical  value  to  each  stage  of  disintegration  and  determining  the  average 
stage  of  disintegration  in  any  lot  at  any  given  time  by  multiphdng  the  number  of  worms 
in  each  stage  at  that  time  by  the  value  of  that  stage,  adding  the  products  for  all  stages, 
and  dividing  by  ten.  By  marking  off  vertical  intervals  from  above  do\vnward,  cor- 
responding to  the  nimierical  values  assigned  to  the  different  stages,  as  in  Fig.  3,  the 
average  stage  of  disintegration  can  be  plotted  at  once  by  counting  downward  from 
the  zero  point  the  number  of  spaces  equal  to  its  numerical  value,  or,  in  other  words, 
the  ordinate  of  the  susceptibility  curve  for  any  average  stage  of  disintegration  is  equal 
to  40  minus  the  value  of  that  stage. 

The  determination  of  the  average  stages  of  disintegration  and  of  the  disintegra- 
tion ordinates  for  the  time  i .  30  in  Table  I  will  serve  to  illustrate  the  method  of  pro- 
cedure. The  values  assigned  to  the  different  stages  are:  Stage  I,  o;  Stage  II.  10; 
Stage  III,  20;   Stage  IV,  30;   Stage  V,  40. 

Condition  of  Lot  i :     2  animals  in  Stage  III :    2X20=  40 


3 

u 

u 

u 

IV: 

3X30=    90               Average^ 

5 

a 

u 

u 

V: 

5X40=200               Disinte- 
gration 

330^10  =  33 

Condition  of  Lot  2 : 

8 

u 

u 

u 

I: 

8X  0=     0 

2 

u 

u 

u 

II: 

2X10=    20 

20-J-I0=     2 

Ordinate  for  Lot  i  at  ij  hours  =40  —  33=   7 

Ordinate   "       "    2  "     "        "       =40-   2  =  38 

The  horizontal  distances  of  the  points  of  the  curve  from  the  zero  point  at  the  left 
(abscissae)  in  Fig.  3  represent  lengths  of  time  in  tlie  cyanide,  half-hour  inter\-als, 
the  intervals  at  which  the  condition  of  the  animals  was  recorded  being  indicated  on 
the  axis  of  abscissae. 


82  SENESCENCE  AND  REJUVENESCENCE 

in  cyanide  and  the  death  of  the  last  part  of  the  body  in  the  animals 
of  each  lot.  Thus  the  differences  in  susceptibility  of  two  or  more  lots 
of  worms  are  evident  at  a  glance,  for  the  farther  to  the  right  the 
curve  lies,  the  less  the  susceptibility,  and  vice  versa.  In  Fig.  3,  for 
example,  the  susceptibility  of  the  young  worms,  as  indicated  by 
the  curve  ah,  is  very  much  greater  than  that  of  the  old  worms,  as 
indicated  by  the  curve  cd. 

The  susceptibility  curves  in  the  following  chapters  are  all  drawn 
in  the  same  way  as  those  in  Fig.  3  and  from  data  similar  to  those  in 
Table  I.  In  general  this  method  is  more  convenient  than  the 
indirect  method  described  below,  and  the  results  are  less  likely  to 
be  affected  by  complicating  factors. 

THE  INDIRECT  METHOD 

By  this  method  the  susceptibility  or  physiological  resistance  to 
the  depressing  agent  is  determined  indirectly,  through  the  ability 
of  the  animals  to  become  acclimated  to  a  given  concentration.  In 
general,  but  with  certain  exceptions,  the  ability  of  an  animal  to 
acclimate  to  the  cyanides  or  other  depressing  agents  varies  with  the 
rate  of  metabolism,  that  is,  animals  with  the  higher  rate  live  longer 
than  those  with  a  lower  rate.  In  experiments  by  this  method  a 
concentration  of  the  agent  used  is  determined  which  does  not  kill 
the  animals  directly,  but  allows  more  or  less  acclimation.  The 
concentration  to  be  used  depends  to  some  extent  upon  the  condition 
of  the  animals  to  be  tested.  For  those  with  a  high  rate  of  metab- 
olism higher  concentrations  are  necessary  than  for  those  with  a 
low  rate.  With  different  temperatures  also  different  concentrations 
must  be  used.  For  Planaria  dorotocephala  at  temperatures  near 
20°  C,  potassium  cyanide,  0.00002-0.00004  mol-  (0.00013-0.00026 
per  cent)  serves  in  most  cases  and  i-i|-  per  cent  alcohol  or  0.2- 
o .  3  per  cent  ether  gives  essentially  the  same  results.  The  details 
of  technique  and  certain  complicating  and  limiting  factors  have 
been  considered  elsewhere  (Child,  '11,  '13a,  '14a). 

The  results  of  such  experiments  are  best  presented  in  graphic 
form.  Fig.  4  shows  the  different  ability  of  old  and  young  indi- 
viduals of  Planaria  dorotocephala  to  acclimate  to  if  per  cent  alco- 
hol.    Each  small  interval  represents  2  per  cent  of  the  total  number 


THE  PROBLEM  AND  METHODS  OF  INVESTIC.A  1  iON         83 

of  worms  in  each  lot  compared,  and  each  horizontal  interval  repre- 
sents one  day.  Each  point  of  the  curve  represents  the  percentages 
of  worms  intact  at  a  given  time  during  the  experiment.  Each 
curve  is  plotted  from  fifty  worms  and  from  examinations  two  days 
apart.  The  curve  ab  shows  the  survival  time  of  old,  large  indi- 
viduals, the  curve  ac,  that  of  fifty  younger  individuals  of  medium 
size. 

It  will  be  noted  that  the  relation  between  survival  time  and  rate 
of  metaboHsm  is  the  opposite  of  that  observed  by  the  direct  method. 


Fig.  4. — Planaria  doroloccphala:  death  curves  of  young  and  old  animals  in  i .  5  per 
cent  alcohol;  ab,  curve  of  fifty  old  worms;  ac,  curve  of  fifty  young  worms. 

Here  the  younger  animals  with  the  higher  rate  live  much  longer 
than  the  older  with  the  lower  rate.  It  is  also  evident  that  the  rela- 
tion between  surface  and  volume  in  animals  of  different  size  plays 
no  part  in  the  result,  for  the  smaller  animals  live  longer  than  the 
larger.  The  results  obtained  with  cyanide  and  other  depressing 
agents,  and  even  with  low  temperatures,  are  essentially  the  same. 
The  difference  in  the  ability  of  the  animals  to  become  acclimated 
to  low  concentrations  of  depressing  agents  is  apparent,  not  merely 
in  the  length  of  hfe,  but  in  the  motor  activity.  The  primary  effect 
of  the  depressing  agent  is  greater  upon  the  young  than  uj>on  the 


84 


SENESCENCE  AND  REJUVENESCENCE 


old  animals,  but  the  young  animals  recover  more  rapidly  and  more 
completely  under  the  depressing  conditions,  and  within  a  few  days 
are  very  evidently  more  active  than  the  old. 

The  relation  between  the  capacity  for  acclimation  and  rate  of 
metabolism  can  be  demonstrated  very  clearly  by  combining  the 
effect  of  depressing  agents  with  that  of  different  temperatures. 
Animals  in  low  concentration  of  cyanide  or  alcohol  are  less  capable 
of  acclimation  and  die  earlier  at  lower  than  at  higher  temperatures. 
Fig.  5  shows  the  results  in  an  experiment  of  this  sort.     The  curves 


Fig.  5. — Planaria  dorotocephala:  death  curves  of  full-grown  animals  in  1.5 
per  cent  alcohol  at  8°-io°  C.  {ah)  and  at  20°  C.  {ac). 

are  plotted  in  the  same  way  as  in  Fig.  4.  The  curve  ab  is  the 
death  curve  of  forty  animals  in  i^  per  cent  alcohol  at  a  temperature 
of  8°-io°  C,  the  curve  ac  that  of  forty  animals  of  the  same  size  and 
from  the  same  stock  in  i|  per  cent  alcohol  at  20°  C.  The  greater 
resistance  of  the  animals  at  the  higher  temperature  is  clearly 
apparent. 

But  that  the  rate  of  metabolism  is  not  the  only  factor  involved 
in  acclimation  to  depressing  agents  is  evident  from  the  comparison 
of  starved  with  well-fed  animals.  In  experiments  to  be  described 
in  following  chapters  it  will  be  shown  that  in  animals  undergoing 


THE  PROBLEM  AND  METHODS  OF  LW^STIGATIOX        85 

reduction  from  starvation  the  rate  of  metabolism  gradually  rises, 
so  that  a  starved  animal,  reduced  to,  let  us  say,  one-half  its  size  at 
the  beginning  of  the  experiment,  has  a  much  higher  rate  of  metab- 
olism than  well-fed  animals  of  its  original  size  and  about  the  same 
rate  as  well-fed  animals  of  its  reduced  size.  But  the  reduced  animal 
has  to  a  large  extent  lost  its  ability  to  become  acclimated  to  depress- 
ing agents  and  conditions,  and  in  spite  of  its  high  rate  of  metabohsm 
is  more  susceptible  to  low  concentrations  of  cyanide,  alcohol,  etc., 
and  also  to  low  temperatures,  than  well-fed  animals  of  the  same  size 
as  itself,  and  shows  about  the  same  susceptibiHty  as  well-fed  animals 
of  its  original  size,  although  these  possess  a  much  lower  rate  of 
metabohsm.  In  other  words,  the  animal  which  is  using  its  own 
structural  substance  as  a  source  of  energy  is  much  less  able  to 
acchmate  itself  to  depressing  conditions  than  an  animal  with  the 
same  rate  of  metabolic  reaction  but  with  abundant  nutritive  ma- 
terial. Consequently,  it  is  impossible  to  determine  the  differences 
in  rate  of  metabolism  between  well-fed  and  starved  animals  by  the 
indirect  method.^ 

In  some  cases  also,  where  the  differences  of  size  between  animals 
compared  are  very  great,  the  smaller  animals  die  of  starvation 
before  the  larger  animals  undergo  sufficient  reduction  to  reach  the 
death  point,  but  this  occurs  only  where  the  differences  are  extreme. 

In  general  the  indirect  method  is  of  value  as  a  means  of  confirm- 
ing the  results  of  the  direct  method,  and  it  can  be  applied  to  certain 
forms  where  the  direct  method  may  be  complicated  by  the  relation 
between  surface  and  volume.  The  concentration  to  be  used  for 
either  method  must  of  course  be  determined  for  each  species. 

OTHER  METHODS 

There  are  other  physiological  differences  between  young  and 
old  organisms  besides  the  rate  of  metabohsm.  In  many  cases 
marked  differences  in  motor  activity  exist  between  young  and  old 

'  Since  I  was  unaware  of  this  relation  between  the  capacity  for  acclimation  and 
the  nutritive  condition  at  the  time  of  my  earlier  experiments  on  rejuvenescence  by 
starvation,  the  use  of  the  indirect  method  in  those  experiments  led  to  incorrect  con- 
clusions concerning  the  changes  in  rate  during  starvation  (Child,  '11,  pp.  S47~SS)» 
but  correction  has  been  made  in  a  later  paper  (Child,  '14a).  The  reader  is  also 
referred  to  chapter  vii  below. 


86  SENESCENCE  AND  REJUVENESCENCE 

animals,  and  the  capacity  of  an  individual  for  growth  and  develop- 
ment must  be  regarded  as  to  some  extent  a  criterion  of  its  youth  or 
age.  If  we  can  induce  an  animal  to  pass  through  an  indefinite 
number  of  agamic  generations,  each  of  which  shows  the  same  vigor 
and  the  same  cycle  of  growth  and  development,  we  must  conclude, 
either  that  senescence  does  not  occur  in  such  cases,  or  else  that 
there  is  a  periodic  rejuvenescence  associated  in  some  way  with  the 
reproductive  process  or  other  processes,  and  we  may  use  the  sus- 
ceptibihty  methods  to  determine  which  of  these  two  alternatives 
is  correct.  In  at  least  many  organisms,  probably  in  all,  if  the 
nutritive  and  other  conditions  are  controlled  with  sufficient  care, 
the  percentage  increment  of  growth  decreases  with  advancing 
age  and  serves  as  a  more  or  less  exact  indication  of  physiological 
condition,  though  subject  to  periodic  or  irregular  variation.  In 
those  forms  which  attain  or  approach  a  more  or  less  definite  limit 
of  size,  size  itself  under  the  normal  or  usual  conditions  of  existence 
may  serve  as  a  criterion  of  age,  since  the  size  of  the  organism  indi- 
cates approximately  its  position  in  the  life  cycle. 

The  morphological  characters,  whether  those  of  the  cells  or  of 
the  organism  as  a  whole,  may  serve  as  an  indication  of  the  youth  or 
age  of  the  individual,  but  it  must  be  remembered  that  senescence 
and  rejuvenescence  are  primarily  physiological  rather  than  morpho- 
logical changes,  and  that  morphological  characters  are  available 
as  criteria  only  so  far  as  we  have  learned  by  experience  that  cer- 
tain of  them  are  characteristic  of  organisms  which  we  can  distin- 
guish by  other  means  as  physiologically  young  or  old.  In  man  and 
the  higher  animals  the  morphological  differences  between  youth  and 
age  are  clearly  evident,  but  for  many  of  the  lower  forms  this  is  not 
the  case,  although  sufficiently  minute  anatomical  or  histological 
investigation  would  probably  disclose  some  characteristic  differ- 
ences. If  these  various  criteria  of  youth  and  age  are  all  valid,  we 
should  find  that,  so  far  as  they  can  be  applied  to  any  particular  case, 
they  lead  to  essentially  the  same  conclusion  as  regards  that  case. 
As  a  matter  of  fact,  they  are  very  generally  in  agreement,  but 
there  are  various  cases  in  which  one  or  another  of  these  criteria 
leads  to  conclusions  different  from  the  others.  Some  of  these 
cases  will  be  considered  in  later  chapters. 


THE  PROBLEM  AND  METHODS  OF  IN\^STIGATION        87 

We  are  accustomed,  and  experience  justifies  the  custom,  to 
measure  age  in  man  and  the  higher  vertebrates  by  the  time  ehipsed 
since  birth.  We  say  that  the  individual  is  a  certain  number  of 
years  old,  and  from  the  age  in  years  we  can  reach  fairly  definite 
conclusions  as  to  physiological  condition,  i.e.,  physiological  age. 
In  many  of  the  lower  forms,  however,  senescence  does  not  neces- 
sarily proceed  at  an  approximately  definite  rate.  In  such  organisms 
the  time  elapsed  since  the  beginning  of  development  does  not  afford 
any  measure  of  the  physiological  age  attained,  for,  as  the  following 
chapters  will  show,  the  organism  has  not  necessarily  continued  to 
grow  old  during  all  of  that  time.  Thus  it  is  possible  that  among 
members  of  the  same  brood,  beginning  development  at  the  same 
time,  some  may  attain  a  much  greater  physiological  age  in  a  given 
length  of  time  than  others.  In  short,  we  cannot  measure  age  in 
all  organisms  in  terms  of  time. 

And,  finally,  we  may  attempt  to  modify  the  processes  of  senes- 
cence and  rejuvenescence  and  so  to  gain  further  insight  into  their 
nature.  The  influence  of  external  conditions  and  of  quantity 
and  quality  of  nutrition  may  be  determined.  We  may  e.xpect  to 
find  that  factors  which  influence  the  fundamental  metabolic  pro- 
cesses or  the  structural  substratum  will  affect  the  course  or  char- 
acter of  senescence  and  rejuvenescence  in  one  way  or  another  if 
their  action  continues  for  a  sufficiently  long  time.  In  many  of 
the  lower  forms  reproduction  may  be  induced  experimentally  by 
the  isolation  of  pieces  of  the  body,  which  undergo  a  reorganization 
into  complete  new  individuals.  These  experimental  reproductions, 
wherever  they  can  be  induced  to  occur,  affect  the  course  of  senes- 
cence and  as  a  matter  of  fact  bring  about  a  greater  or  less  degree 
of  rejuvenescence.  The  problem  is  then  accessible  to  analytic 
investigation  in  the  lower  forms,  and  the  results  of  such  investiga- 
tion afford  a  firm  foundation  for  the  interpretation  of  the  phe- 
nomena of  senescence  and  rejuvenescence  in  the  higher  organisms, 
where  they  are  less  accessible  to  experimental  methods. 

REFERENCES 

Alexander,  F.  G.,  and  Cserna,  S. 

1913.     "Einfluss  der  Narkose  auf  den  Gaswechsel  des  Gehirns."  Biochem. 
Zeitschr.,  LIII. 


88  SENESCENCE  AND  REJUVENESCENCE 

Bernard,  Cl. 

1875.     Leqons  sur  les  anesthetiques,  etc. 

Carlson,  A.  J. 

1907.  "On  the  Action  of  Cyanides  on  the  Heart,"  Am.  Jour,  of  Physiol., 
XIX. 

Child,  C.  M. 

1911.  "A  Study  of  Senescence  and  Rejuvenescence  Based  on  Experiments 
with  Planarians,"  Arch.  J.  Entwickelungsmech.,  XXXI. 

1913a.  "Studies  on  the  Djoiamics  of  Morphogenesis  and  Inheritance  in 
Experimental  Reproduction:  V.  The  Relation  between  Resist- 
ance to  Depressing  Agents  and  Rate  of  Reaction  in  Planaria 
dorotocephala  and  Its  Value  as  a  Method  of  Investigation,"  Jour. 
ofExp.Zool.,XlV. 

1913&.  "Studies  on  the  Dynamics,  etc.:  VI.  The  Nature  of  the  Axial 
Gradients  in  Planaria  and  Their  Relation  to  Antero-posterior 
Dominance,  Polarity  and  Symmetry,"  Arch.  f.  Entwickelungs- 
mech., XXXVII. 

1914a.  "Starvation,  Rejuvenescence  and  Acclimation  in  Planaria  doro- 
tocephala," Arch.  f.  Entwickelungsmech.,  XXXVIII. 

1914&.  "Studies,  etc.:  VII.  The  Stimulation  of  Pieces  by  Section  in 
Planaria  dorotocephala,"  Jour,  of  Exp.  Zool.,  XVI. 

Drzewina,  Anna,  et  Bohn,  G. 

1913.  " Anoxybiose  et  polarite," Comp.  rend.  Acad.  Sci.  Paris,  CXXXVI. 

Dubois,  R. 

1894.     Anesthesie  physiologique. 

Gasser,  H.  S.,  and  Loevenhart,  A.  S. 

1914.  "The  Mechanism  of  Stimulation  of  the  Medullary  Centers  by 
Decreased  Oxidation."    Jour,  of  Pharm.  and  Exp.  Therap.,  V. 

Geppert,  J. 

1889.  "Uber  das  Wesen  der  Blausaurevergiftung,"  Zeitschr.  f.  kiln. 
Med.,  XV. 

Grove,  W.  E.,  and  Loevenhart,  A.  S. 

1911.  "The  Action  of  Hydrocyanic  Acid  on  the  Respiration  and  the 
Antagonistic  Action  of  Sodium  lodosobenzoate,"  Jour,  of  Pharm. 
and  Exp.  Therap.,  HI. 

HOBER,  R. 

1910.  "Die  physikalisch-chemischen  Vorgange  bei  der  Erregung:  Sam- 
melreferat,"  Zeitschr.  f.  allgeni.  Physiol.,  X. 

Jennings,  H.  S. 

1913.     "The  Effect  of  Conjugation  in  Paramecium,"  Jour,  of  Exp.  Zool., 
XIV. 
Kastle,  J.  H.,  and  Loevenhart,  A.  S. 

1901.  "On  the  Nature  of  Certain  of  the  Oxidizing  Ferments,"  Am. 
Chem.  Jour.,  XXVI. 


THE  PROBLEM  AND  METHODS  OF  INVESTIGATION        89 

KisCH,  B. 

1913.  "Untersuchungen  iiber  Narkose,"  Zeitschr.  f.  Biol,  LX. 

LlLLIE,  R.  S. 

1912a.  "Antagonism  between  Salts  and  Anesthetics:  I.  On  the  Con- 
ditions of  the  Antistimulating  Action  of  Anesthetics,  with  Obser\-a- 
tions  on  Their  Protective  or  Antitoxic  Action,"  Am.  Jour,  of 
Physiol.,  XXIX. 

191 2&.  "Antagonism,  etc.:  II.  Decrease  by  Anesthetics  in  the  Rate  of 
Toxic  Action  of  Pure  Isotonic  Salt  Solution  on  Unfertilized  Star- 
fish and  Sea  Urchin  Eggs,"  Am.  Jour,  oj  Physiol.,  XXX. 

1913a.  "Antagonism,  etc.:  III.  Further  Observations,  Showing  Parallel 
Decrease  in  the  Stimulating,  Permeability-increasing  and  Toxic 
Actions  of  Salt  Solutions  in  the  Presence  of  Anesthetics,"  Am. 
Jour,  of  Physiol.,  XXXI. 

19136.  "The  Physico-chemical  Conditions  of  Anesthetic  Action,"  Sci- 
ence, XXX  VH. 

1914.  "Antagonism,  etc.:  IV.  Inactivation  of  Hypertonic  Sea-Water 
by  Anesthetics,"  Jour,  of  Exp.  ZooL,  XVI. 

LOEB,  J. 

1909.  Die  chemische  Entwicklungserregung  des  tierischen  Eies.      Berlin. 

1910.  "Die  Hemmung  verschiedener  Giftwirkungen  auf  das  befruchtete 
Seeigelei  durch  Hemmung  der  Oxydationen  in  demsclbcn,"  Bio- 
chem.  Zeitchr.,  XXIX. 

LoEB,  J.,  and  Lewis,  W.  H. 

1902.  "On  the  Prolongation  of  the  Life  of  the  Unfertilized  Eggs  of  the 
Sea  Urchin  by  Potassium  Cyanide,"  Am.  Jour,  of  Physiol.,  VI. 

LoEB,  J.,  und  Wasteneys,  H. 

1910.     "Warum  hemmt  Natriumcyanide  die  Giftwirkung  einer  Chlorna- 

triunlosung  fiir  das  Seeigelei?"  Biochem.  Zeitschr.,  XX\TII. 
1913a.  "Is  Narcosis  Due  to  Asphyxiation?"  Jour,  of  Biol.  Chcm.,  XI\'. 
19136.    "Narkose   und   Sauerstoffverbrauch,"   Biochem.   Zeitschr.,   L\T. 

Lyon,  E.  P. 

1902.  "Effects  of  Potassium  Cyanide  and  of  Lack  of  Oxygen  upon  the 
Fertilized  Eggs  and  the  Embryos  of  the  Sea  Urchin  {Arhacia 
punctulata),"  Am.  Jour,  of  Physiol.,  VII. 

1904.  "Rhythms  of  Susceptibility  and  of  Carbon  Dioxide  Production 
in  Cleavage,"  Am.  Jour,  of  Physiol.,  XL 

]\Iathews,  a.  p. 

1906.     "A  Note  on  the  Susceptibility  of  Segmenting  Arbacia  and  As- 

terias  Eggs  to  Cyanides,"  Biol.  Bull.,  XL 
1910.     "The  Action  of  Ether  on  Anaerobic  Animal  Tissue,"  Jour,  of 

Pharm.  and  Exp.  Therap.,  II. 
1913.     "The  Nature  of  Irritability  and  the  Action  of  Anesthetics," 

Science,  XXXVH  (Proc.  Am.  Chcm.  Soc). 


90  SENESCENCE  AND  REJUVENESCENCE 

Mathews,  A.  P.,  and  Walker,  S. 

1909.  "The  Action  of  Cyanides  and  Nitriles  on  the  Spontaneous  Oxida- 
tion of  Cystein, "  Jour,  of  Biol.  Chem.,  VI. 

Maupas,  E. 

1888.  "Recherches  experimentales  sur  la  multiplication  des  infusories 
cilies,"  Arch,  de  zool.  exp.,  (2),  VI. 

1889.  "La  rajeunissement  karyogamique  chez  les  cilies,"  Arch,  de  zool. 
exp.,  (2),  VII. 

Meyer,  H. 

1899.  "Zur  Theorie  der  Alkoholnarkose :  Erste  Mitteilung.  Welche 
Eigenschaft  der  Anasthetica  bedingt  ihre  narkotische  Wirkung?" 
Arch.  f.  exp.  Pathol,  u.  Phartn.,  XLII. 
1901.  "Zur  Theorie,  etc.:  Dritte  Mitteilung.  Einfluss  wechselnder 
Temperatur  auf  Wirkungstarke  und  Teilungscoefficient  der  Nar- 
cotica,"  Arch.f.  exp.  Pathol,  u.  Pharm.,  XL VI. 
MmoT,  C.  S. 

1908.     The  Problem  of  Age,  Growth  and  Death.    New  York. 

Overton,  E. 

1901.    Stiidieniiher  dieNarkose.    Jena. 

Richards,  A.  N.,  and  Wallace,  G.  B. 

1908.     "The  Influence  of  Potassium  Cyanide  upon  Proteid  Metabolism," 
Jour,  of  Biol.  Chem.,  IV. 
SCHULTZ,  E. 

1904.  "tJber  Reduktionen:  I.  tjber  Hungererscheinungen  bei  Planaria 
lactea,"  Arch.f.  Entwickelungsmech.,  XVIII. 

1908.     "tJber  umkehrbare  Entwicklungsprozesse  und  ihre  Bedeutung  fiir 
eine  Theorie  der  Vererbung,"  Vortr.  und  Aufs.  u.  Entwickelungs- 
mech., IV. 
Tashlro,  S. 

1913a.  "Carbon  Dioxide  Production  from  Nerve  Fibers  When  Resting 
and  When  Stimulated;  A  Contribution  to  the  Chemical  Basis 
of  Irritability,"  Am.  Jour,  of  Physiol.,  XXXII. 

19135.  "A  New  Method  and  Apparatus  for  the  Estimation  of  Exceedingly 
Minute  Quantities  of  Carbon  Dioxide,"  Am.  Jour,  of  Physiol., 
XXXII. 
Traube,  J. 

1904a.  "Theorie  der  Osmose  und  Narkose,"  Arch.  f.  d.  ges.  Physiol.,  CV. 

19046.  "Der  Oberflachendruck  und  seine  Bedeutung  im  Organismus," 
Arch.f.  d.  ges.  Physiol.,  CV. 

1908.  "Die  osmotische  Kraft,"  Arch.f.  d.  ges.  Physiol.,  CXXIII. 

1910.  "Die  Theorie  des  Haftdruckes  (Oberflachendrucks)  und  ihre  Bedeu- 

tung fur  die  Physiologic,"  Arch.f.  d.  ges.  Physiol.,  CXXXII. 

1911.  "Die  Theorie  des  Haftdruckes  (Oberflachendrucks),  V,"  Arch. 
f.  d.  ges.  Physiol.,  CXL. 

1913.     "Theorie  der  Narkose,"  Arch.f.  d.  ges.  Physiol.,  CLIII. 


THE  PROBLEM  AND  METHODS  OF  INVESTIGATION         91 

Vernon,  H.  M. 

1906.     "The  Conditions  of  Tissue  Respiration,"  Jour,  of  Physiol.,  XXXV. 

1909.  "The  Conditions  of  Tissue  Respiration.     Part  III.     The  Action 
of  Poison,"  Jour,  of  Physiol.,  XXXIX. 

1910.  "The  Respiration  of  the  Tortoise  Heart  in  Relation  to  Functional 
Activity,"  Jour,  of  Physiol.,  XL. 

1913.     "The  Changes  in  the  Reactions  of  Growing  Organisms  to  Nar- 
cotics," Jour,  of  Physiol.,  XL VII. 

Verworn,  M. 

1903.     Die  Biogenhypothese.     Jena. 

191 2.  Narkose.     Jena. 

1913.  Irritability.     New  Haven,  Conn. 

Warburg,  0. 

1910a.  "Uber  die  Oxydationen  in  lebenden  Zellen  nach  Versuchen  am 

Seeigelei,"  Zeitschr.  f.  physiol.  Chem.,  LXVI. 
1910&.  "Uber  Beeinfliissung  der  Oxydationen  in  lebenden  Zellen  nach 

Versuchen  an  roten  Blutkorperchen,"  Zeitschr.  f.  physiol.  Chcm., 

LXIX. 
1910C.  "Uber  Beeinfliissung  der  Sauerstoffatmung,"  Zeitschr.  f.  physiol. 

Chem.,  LXX. 
1911a.  "Uber  Beeinfliissung,  etc.:    II.  Mitteilung.     Eine  Beziehung  zur 

Constitution,"  Zeitschr.  f.  physiol.  Chejn.,  LXXI. 
19116.  "  Untersuchungen  iiber  die  Oxydationsprozesse  in  Zellen,"  MUn- 

chener  mcd.  Wochenschr.,  LVII. 
1912a.  "Untersuchungen,  etc.,  II,"  MUnchener  nied.  Wochenschr.,  LMII. 
191 26.  "Uber    Beziehungen    zwischen   Zellstruktur   und    biochemischen 

Reaktionen,"  Arch.  f.  d.  ges.  Physiol.,  CXLV. 
1913.     "Uber   die   Wirkung   der   Struktur   auf  chcmische  Vorgiinge  in 

Zellen."     Jena. 
1914a.  "Uber  Verbrennung  der  Oxalsaure  an  Blutkohle  und  Hemmung 

dieser  Reaktion  durch  indifi'erente  Narkotika,"  Arch.  f.  d.  ges. 

Physiol.,  CLIV. 
19145.  "Uber  die  Empfindlichkeit  der  Sauerstoffatmung  gegeniiber  in- 

differenten  Narkotika,"  Arch.  f.  d.  ges.  Physiol.,  CLVIII. 
1914c.   "Beitriige  zur  Physiologic  der  Zelle,  insbesondere  iiber  die  Ox>'da- 

tionsgeschwindigkeit  in  Zellen,"  Ergebn.  d.  Physiol.,  XI\'. 

Winterstein,  H. 

1902.     "Zur  Kenntnis  der  Narkose,"  Zeitschr.  f.  allgcm.  Physiol.,  I. 
1905.     "Warmeliihmung  und  Narkose,"  Zeitschr.  f.  allgcm.  Physiol.,  V. 

1913.  "Beitriige  zur  Kenntnis  der  Narkose:  I.  Mitteilung.  Kritische 
Ubersicht  iiber  die  Beziehungen  zwischen  Narkose  und  Sauer- 
stoffatmung," Biochcm.  Zeitschr.,  LI. 

1914.  "Beitriige,  etc.:  II.  Mitteilung.  Der  Kintluss  der  Narkose  auf 
den  Gaswcchsel  des  Froschriickcnniarks,"  Biochcm.  Zeitschr.,  LXI. 


CHAPTER  IV 

AGE  DIFFERENCES  IN  SUSCEPTIBILITY  IN  THE  LOWER 

ANIMALS 

THE  EXPERIMENTAL  MATERIAL 

Three  species  of  fresh-water  planarians,  Planaria  dorotocephala, 
P.  maculata,  and  P.  velata,  have  constituted  the  chief  material  for 
the  more  extended  investigations.  P.  dorotocephala  is  found  in 
great  abundance  in  various  parts  of  the  United  States,  chiefly  in 
springs  and  the  streams  issuing  from  them.  In  nature  the  animals 
usually  attain  a  length  of  twenty  to  twenty-five  millimeters,  but 
in  the  laboratory  with  abundant  food  may  reach  double  that 
length. 

The  body,  like  that  of  most  turbellaria,  is  dorso-ventrally 
flattened ;  the  body- wall  consists  of  a  one-layered  ciliated  ectoderm 
beneath  which  lie  longitudinal  and  transverse  muscle  layers  and 
in  the  spaces  between  the  internal  organs  a  parenchymal  tissue. 
A  pigment  layer  beneath  the  dorsal  ectoderm  gives  the  dorsal  sur- 
face a  deep-brown  color,  the  ventral  surface  being  much  less  deeply 
pigmented.  The  chief  features  of  the  internal  anatomy  are  indi- 
cated in  Fig.  6.  The  central  nervous  system  consists  of  a  pair  of 
cephalic  ganglia  beneath  the  eyes  and  two  longitudinal  cords  (ns) 
which  give  off  branches  and  are  connected  by  commissures.  The 
chief  sense-organs  are  the  eyes,  consisting  of  pigment  cups  con- 
taining sensory  cells  and  the  lateral  pointed  cephalic  lobes,  which 
are  organs  of  chemical  sense.  The  margins  of  the  head  and  body 
are  also  sensitive  tactile  organs. 

The  mouth  (m)  lies  ventrally  in  the  middle  of  the  body  and  opens 
into  a  pharyngeal  pouch  containing  a  tubular  pharynx  (ph).  At 
its  anterior  end  the  pharynx  opens  into  the  alimentary  tract  which 
consists  of  three  main  branches  (a/)  and  many  secondary  branches. 
A  diffuse  branching  excretory  system  is  also  present,  but  not  shown 
in  the  figure.  Under  the  usual  conditions  the  animals  do  not 
become  sexually  mature,  and  sexual  organs  if  present  at  all  do 
not  develop  beyond  very  early  stages. 

92 


AGE  DIFFERENCES  IN  SUSCEPTIBILITY 


93 


The  general  plan  of  internal  structure  of 
other  related  species  is  much  the  same,  but 
they  differ  in  shape  and  general  appearance. 
Planaria  macidata  (Fig.  7)  does  not  attain  as 
large  a  size  as  P.  dorotocephala  and  is  less 
active.  The  head  differs  in  shape  from  that 
of  P.  dorotocephala  and  the  pigment  is  dis- 
tributed in  large  spots.  P.  velata  (Fig.  8)  is 
more  slender,  somewhat  less  flattened,  and 
without  the  pointed  cephalic  lobes.  The 
younger  worms  are  almost  black,  but  become 
light  gray  with  advancing  age. 

Various  other  flatworms,  protozoa,  the 
fresh-water  hydra,  and  several  marine 
hydroids  have  been  used  in  comparative  ex- 
periments. 

AGE   DIFFERENCES   IN   SUSCEPTIBILITY   IN 

Planaria  maculata 

Animals  of  this  species  kept  in  the  labora- 
tory and  fed  become  sexually  mature  and 
deposit  egg  capsules  containing  fertilized 
eggs,  and  from  these  capsules  the  young 
worms  emerge  in  about  four  weeks  at 
ordinary  temperatures.  When  first  hatched 
the  young  worms  possess  the  form  of  the 
adult,  but  are  only  about  two  millimeters  in 
length,  while  in  my  stock  the  old,  sexually 
mature  worms,  which  were  laying  eggs,  were 
about  twelve  millimeters  long. 

Fig.  9  shows  the  susceptibility  curves  (see 
pp.  80-82)  of  young  and  old  animals  of 
this  species  to  potassium  cyanide,  o.ooi  mol. 
The  curve  ah  gives  the  susceptibility  for  ten 
newly  hatched  worms,  the  curve  cd,  that 
for  ten  full-grown  sexually  mature  worms 
about    twelve    millimeters    in    length.     The 


j^fl'' 


-p/i 


VI 


Fig.  6. — Planaria 
dorotocephala:  w, mouth; 
ph,  phar>Tix;  al,  alimcn- 
tar>-  tract;  us,  nervous 
system. 


94 


SENESCENCE  AND  REJUVENESCENCE 


&  fc 


u 


susceptibility  of  the  newly  hatched  worms  is  much  greater  than 
that  of  the  full-grown  animals,  disintegration  of  the  former  being 

far  advanced  before  it  begins  in 
the  latter.  Since  susceptibility  meas- 
ured by  the  higher  concentrations  of 
the  direct  method  varies  with  rate 
of  metabolism,  the  young  animals 
must  have  a  much  higher  rate  than 
the  old. 

But  the  method  enables  us  to  dis- 
tinguish age  differences  in  rate  of 
metabolism  which  are  very  much  less 
than  these.  In  Fig.  lo  the  curve  ab 
shows  the  susceptibility  of  ten  worms 
hatched  within  the  twenty-four  hours 
preceding  the  beginning  of  the  experi- 
ment, and  the  curve  cd  the  suscepti- 
biUty  of  ten  animals  four  days  after 
hatching  and  without  food.  Here 
the  difference  in  size  between  the 
animals  of  the  two  lots  is  much 
less  than  in  the  preceding  case,  the 
younger  worms  being  two  millimeters, 
the  older  three  and  one-half  milli- 
meters long.  The  figure  shows  that 
the  susceptibility  of  the  newly 
hatched  animals  is  consider- 
ably greater,  i.e.,  their  rate  of  metab- 
olism is  higher  than  that  of  the 
animals  four  days  after  hatching. 
Since  the  differences  in  susceptibility 
as  shown  in  Fig.  lo  are  considerable 
for  four  days'  time,  it  is  evident  that  the  rate  of  metabolism  must 
decrease  rapidly  after  hatching. 

The  young  worms  are  capable  of  movement  before  they  emerge 
from  the  egg  capsules,  and  by  opening  the  capsules  with  fine  needles 
it  is  possible  to  obtain  young  worms  of  various  stages  before  hatch- 


FlGS. 

and  P. 


7,  8. — Planaria  maculata 
velata. 


AGE  DIFFERENCES  IN  SUSCEPTIBILITY 


95 


ing.  A  comparison  of  the  resistance  to  cyanide  of  unhatched 
worms  capable  of  movement  with  that  of  worms  just  hatched 
shows,  as  in  Fig.  lo,  that  the  younger  worms  have  the  higher  rate 
of  metabohsm,  although  in  this  case  also  the  difference  in  age  meas- 
ured by  time  is  no  more  than  a  few  days. 

But  it  is  only  during  these  earlier  stages  of  the  life  cycle  that 
the  rate  of  metabolism  changes  appreciably  during  such  short 
intervals  of  time. 
The  rate  of  metab-  Stages 
olism  decreases  most 
rapidly  during  the 
earlier  stages,  and  as 
development  ad- 
vances the  decrease 
in  rate  for  a  given 
time  interval  becomes 
always  less.  In  ani- 
mals eight  or  nine 
milHmeters  in  length, 
for  example,  the 
differences  in  rate  of 
metabolism  for  an  in- 
terval of  two  or  three 
weeks,  under  ordinary 
conditions  of  nutri- 
tion and  temperature, 
and  in  many  cases 
for  a  much  longer 
interval,     are     no 

greater  than  the  differences  shown  in  Fig.  lo  for  an  interval  of  four 
days  immediately  after  hatching.  In  still  older  animals  the 
decrease  in  rate  of  metabolism  under  constant  conditions  is  even 
slower. 

In  Fig.  1 1  the  susceptibilities  of  two  lots  of  large  old  worms  are 
compared.  The  curve  ah  is  from  ten  worms  twelve  millimeters  in 
length,  and  cd  from  ten  worms  sixteen  to  eighteen  millimeters  in 
length.     These  worms  were  collected  from  their  natural  habitat 


Hours 


4i 


j< 


Fig.  9. — Susceptibility  of  Planaria  viaculata  to 
KCN  o.ooi  mol.:  ab,  recently  hatched  worms;  cd, 
full-grown,  se.xually  mature  worms. 


96 


SENESCENCE  AND  REJUVENESCENCE 


Stages  -v 


II 


III 


IV 


at  this  size  and  it  is  impossible  to  say  whether  the  larger  worms  are 
older  in  point  of  time  than  the  smaller.  They  have,  however, 
attained  a  stage  of  growth  and  development  which  under  anything 
approaching  natural  conditions  could  be  reached  by  the  smaller 
worms  only  after  at  least  some  weeks. 

The  larger,  physiologically  older  worms  begin  to  disintegrate 
two  hours  later  and  also  complete  their  disintegration  one  and  one- 
half  hours  later  than  the  smaller  ones. 
In  other  words,  their  survival  time  is 
about  one-fifth  greater  than  that  of 
the  smaller  worms.     But  in  Fig.  lo 
above,    the  survival  time  of  worms 
four   days   after   hatching  is  almost 
one-half  greater  than  that  of  worms 
newly  hatched,  that  is,  the  difference 
in   rate   of  metabolism  between  the 
two  lots  of  Fig.  lo,  which  are  only 
four  days  apart,  is  much  greater  than 
that  between  the  two  lots  of  Fig.  ii, 
which  represent  physiological  condi- 
tions several  weeks  apart  in  terms  of 
time.     Clearly  the  rate  of  metabolism 
decreases  very  much  more  slowly  in 
the  larger,  older  worms  than  in  the 
stages  immediately  following  hatch- 
ing.    A  comparison  of  Figs.   lo  and 
II    also   shows,   as  does  Fig.   9,  the 
great  difference  in  susceptibility  be- 
tween   very    young   and    full-grown 
animals. 
These  results  are  in  complete  agreement  with  the  observations 
of  Minot  ('08)  and  others  on  the  rate  of  growth  in  mammals  and 
birds.     The  rate  of  growth  as  measured  by  the  percentage  incre- 
ment is  highest  in  the  youngest  animals  and  decreases  with  advan- 
cing age.     As  Minot  says,  "the  period  of  youth  is  the  period  of  most 
rapid  dechne."     And  now  we  find  this  to  be  true,  not  only  for  the 
rate  of  growth  in  the  higher  animals,  but  for  the  rate  of  metabolism 


Hours 


2± 


34 


Fig.  10. — Susceptibility  of  Pla- 
nar ia  maciilala  to  KCN  o.ooi 
mol.:  ab,  worms  hatched  within 
24  hours;  cd,  worms  four  days 
after  hatching. 


AGE  DIFFERENCES  IN  SUSCEPTIBILITY 


97 


in  such  simple  forms  as  the  planarian  worms.  But  as  will  appear 
more  clearly  in  following  chapters,  time  is  not  a  correct  measure 
of  physiological  age  in  these  lower  forms.  The  animal  which  has 
lived  longer  is  not  necessarily  the  older:  the  older  animal  is  the  one 
which  has  undergone  more  growth  and  development,  but  the 
amount  of  growth  and  development  is  dependent  upon  nutrition, 
temperature,   and   other   external   conditions.     It   is  possible    to 


Stages   • 


II 


III 


R 


Hours  I  234567 

Fig.  II. — Susceptibility  of  Planaria  macidata  to  KCN  o.ooi  mol.:  ah,  worms 
12  mm.  in  length;  cd,  worms  16-18  mm.  in  length. 

measure  the  physiological  age  of  these  animals  in  terms  of  time 
only  when  the  conditions  of  existence  are  controlled. 

Fig.  12  will  serve  to  illustrate  this  point.  In  this  figure  the 
curve  ah  shows  the  susceptibihty  of  ten  worms  nine  millimeters 
long  from  a  stock  raised  in  the  laboratory  from  eggs  and  only  about 
ten  weeks  "old,"  while  the  curve  cb  is  plotted  from  worms  ten  milli- 
meters long,  but  which  had  lived  at  least  a  year.  The  temperature 
was  somewhat  higher  in  this  series  than  in  those  preceding,  and  the 
survival  times  are  therefore  shorter  than  they  would  be  for  animals 
of  this  age  at  the  temperature  of  the  other  series. 


98 


SENESCENCE  AND  REJUVENESCENCE 


Stages    • 


The  worms  which  are  so  much  "older"  in  point  of  time  show 
only  a  slightly  greater  resistance,  i.e.,  a  shghtly  lower  rate  of  metab- 
olism than  the  worms  of  the  "younger"  lot.  As  a  matter  of  fact, 
the  worms  of  the  curve  cb  had  been  considerably  older  physiologi- 
cally at  an  earHer  period  than  they  were  at  the  time  when  the 
comparison  was  made  and  had  been  undergoing  rejuvenescence 
in  consequence  of  reduction.     We  cannot  measure  the  age  of  such 

organisms  in  terms  of 
time  unless  we  know 
that  they  have  been 
growing  old  without 
interruption,  and  even 
then  the  rate  of  senes- 
cence may  vary  with 
conditions. 

On  the  other  hand, 
size,  or,  more  strictly, 
length — for  in  the  later 
stages  the  growth  is 
largely  a  growth  in 
length — is  under  the 
usual  conditions  and 
within  certain  limits,  a 
fairly  good  criterion  of 
physiological  age. 
Barring  individual  size 
differences,  which  are 
shght,  the  length  of  the 
animal   is   an   index   of 


Hours  1234 

Fig.  12. — Susceptibility  of  Planaria  maculata 
to  KCN  o.ooi  mol.:  ah,  worms  9  mm.  in  length 
and  ten  weeks  after  hatching;  ch,  worms  10  mm.  in 
length  and  at  least  one  year  after  hatching. 


the  amount  of  growth  and  development  which  has  occurred,  and 
we  find  in  general,  as  the  preceding  figures  show,  that  the  longer 
animal  has  a  lower  rate  of  metaboHsm  than  the  shorter.  But  it 
does  not  follow  that  individuals  of  the  same  length  always  possess 
the  same  rate  of  metaboUsm.  A  given  size  may  be  attained  either 
by  growth  from  a  smaller  or  reduction  from  a  larger  size,  and  the 
physiological  condition  of  the  animal  is  not  the  same  in  the  two 
cases.     But  in  a  single  stock,  where  all  individuals  have  been  under 


AGE  DIFFERENCES  IN  SUSCEPTIBILITY  99 

essentially  the  same  conditions  for  a  considerable  period  and  where 
the  animals  are  not  undergoing  fission,  the  length  of  the  worm  is  a 
real  criterion  of  its  physiological  condition,  the  rate  of  metabohsm 
being  lower  in  the  longer  than  in  the  shorter  worms. 

Results  obtained  by  the  direct  method,  such  as  those  presented 
above,  can  be  confirmed  by  the  indirect  or  acclimation  method, 
which  was  described  on  pp.  82-85.  Except  where  the  differences  of 
size  are  extreme,  the  animals  which  have  the  higher  rate  of  metab- 
olism and  die  earlier  in  the  concentrations  of  the  direct  method 
live  longer  than  those  with  the  lower  rate  in  the  low  concentrations 
used  for  the  accKmation  method.  In  other  words,  the  animals 
which  are  larger  and  therefore  physiologically  older  become  less 
readily  and  less  completely  acclimated  to  the  depressing  reagent, 
and  so  die  earlier  than  the  younger  animals.  Since  the  results 
obtained  by  this  method  in  the  present  case  merely  confirm  the 
results  of  the  direct  method,  it  is  unnecessary  to  consider  them  in 
detail. 

AGE  DIFFERENCES  IN  SUSCEPTIBILITY  IN  PlanaHa  dorotoccphala 

In  a  stock  of  Planaria  dorotocephala  collected  from  the  natural 
habitat  of  this  species,  animals  are  found  ranging  in  length  from  four 
or  five  millimeters  up  to  twenty  millimeters  or  more.  Since  there 
is  reason  to  believe  that  sexual  reproduction  does  not  occur,  or  at 
most  occurs  very  rarely  in  this  species  under  natural  conditions  in 
the  localities  which  have  come  under  my  observation,  it  is  certain 
that  at  least  most  of  the  animals  collected  have  arisen  by  fission 
(see  pp.  125,  384-86).  But,  ignoring  for  the  present  the  question  of 
their  origin,  we  should  naturally  regard  the  smaller  worms  in  such 
a  stock  as  the  younger  and  the  larger  as  the  older,  and  we  find  as  a 
matter  of  fact  that  the  same  differences  in  susceptibility  exist  be- 
tween the  larger  and  the  smaller  worms  as  in  P.  maculaia.  This 
difference  is  shown  in  Fig.  3  and  in  Fig.  13.  Fig.  13  gives  the 
susceptibility  curves  of  four  lots  of  ten  worms  each  from  a  stock 
which  had  been  in  the  laboratory  only  one  day.  Curve  ab  shows 
the  susceptibility  of  worms  five  millimeters  in  length,  curve  ac  of 
worms  seven  milKmeters,  curve  ad  of  worms  ten  to  twelve  milli- 
meters, and  curve  ef  of  worms  eighteen  to  twenty  millimeters  in 


lOO 


SENESCENCE  AND  REJUVENESCENCE 


length.     The  survival  times  are  considerably  longer  than  those  in 
Fig.  3  because  of  lower  alkalinity  of  the  water  used. 

A  marked  difference  in  the  susceptibility  of  the  worms  of  differ- 
ent size  appears  in  the  figure.  The  smallest  worms  (curve  ab) 
begin  to  die  and  disintegrate  earlier  and  disintegrate  more  rapidly 
than  the  others,  and  the  susceptibility  in  the  other  lots  decreases 
as  the  size  increases.     In  short,  the  larger  worms  possess  a  lower 

Stages  i  a        e 


Hours 


2\ 


ol  Ai-  ri  ^i  -ri  Si 

31  44  5*  ^4  7l  "4 

Fig.  13. — Susceptibility  of  Planaria  dorotocephala  to  KCN  o.ooi  mol.:  ah, 
worms  5  mm.  in  length;  ac,  worms  7  mm.  in  length;  ad,  worms  10-12  mm.  in  length; 
ef,  worms  18-20  mm.  in  length. 

rate  of  metabohsm  than  the  smaller,  and  in  general  the  rate  of 
metabolism  decreases  with  increasing  size. 

Hundreds  of  animals  of  this  species  have  been  compared  in 
this  way,  with  cyanide,  alcohol,  ether,  etc.,  as  reagents,  and  the 
result  has  been  in  all  cases  essentially  the  same.  Tested  by  the 
acclimation  method,  the  smaller  worms  show  a  greater  capacity 
to  acclimate  to  the  reagent,  i.e.,  a  higher  rate  of  metabolism,  than 
the  larger,  so  that  the  results  of  the  two  methods  check  and  confirm 
each  other.  Moreover,  the  smaller  animals  grow  more  rapidly 
than  the  larger  under  like  conditions  and  are  more  active. 


AGE  DIFFERENCES  IN  SUSCEPTIBILITY  loi 

The  only  possible  conclusion  is  that  in  this  species  individuals 
resulting  from  the  asexual  process  of  fission  show  age  differences 
similar  in  character  to  those  in  the  sexually  produced  individuals 
of  Planaria  macula ta.  In  both  cases  the  rate  of  metabolism  is 
highest  in  the  young  worms  and  decreases  with  advancing  age. 
Later  chapters  will  confirm  this  conclusion  (see  chaps,  v,  vii). 

AGE  DIFFERENCES  IN  SUSCEPTIBILITY  IN  OTHER  FORilS 

In  order  to  determine  whether  age  differences  in  susceptibility 
are  of  general  occurrence  and  of  the  same  sort,  the  susceptibility 
of  young  and  old  individuals  of  a  considerable  number  of  species 
from  different  groups  has  been  compared  by  direct  method.  The 
general  results  of  these  investigations  are  briefly  stated  without 
the  data  of  experiment. 

The  age  differences  in  susceptibility  have  been  determined  for 
various  other  species  of  flatworms.  In  Dendrocoelum  lactcum, 
Phagocata  gracilis,  and  certain  unnamed  species  of  the  Mesoslomidae, 
all  of  which  reproduce  only  sexually,  the  susceptibility  by  the  direct 
method  of  the  young  animals  to  the  cyanides  is  much  greater  than 
that  of  the  old.  In  Planaria  velata,  the  old  worms  break  up  into 
fragments  which  encyst  and  undergo  reconstitution  into  new  indi- 
viduals in  the  cysts  and  later  emerge  as  young  worms  capable  of 
repeating  the  life  cycle.  In  this  species  also  the  susceptibility,  as 
determined  by  the  direct  method,  is  greatest  in  the  young  worms 
after  they  emerge  from  the  cysts,  and  decreases  from  this  stage  on 
until  the  next  fragmentation  (Child,  '13). 

Differences  in  susceptibility  which  are  undoubtedly  connected 
with  physiological  age  have  been  found  in  certain  protozoa  (see 
pp.  141-42).  Among  the  coelenterates  the  fresh-water  hydra 
and  two  species  of  hydroids,  Pennaria  tiarella  (see  Fig.  50,  p.  148) 
and  Corymorpha  palma,  have  been  tested.  In  the  two  hydroids 
the  sexually  produced  young  at  any  stage  after  attaining  the  form 
of  the  adult  show  a  much  greater  susceptibility  than  the  full-grown 
mature  animals.  In  hydra,  se.xually  produced  young  have  not  as 
yet  been  obtained,  but  the  young  animals  asexually  protlucod  show 
a  higher  susceptibility  than  the  parent.  In  the  ctenophore,  Mmmi- 
opsis  leidyi,  the  susceptibility  decreases  with  advancing  physiological 


I02  SENESCENCE  AND  REJUVENESCENCE 

age,  i.e.,  as  growth  and  development  proceed.  Here  the  earliest 
stages  tested  were  young  of  about  five  millimeters  in  diameter. 
Their  susceptibility  is  greater  than  that  of  later  stages  and  very 
much  greater  than  that  of  full-grown  animals.  In  the  course  of 
investigations  not  yet  published  on  several  species  of  oligochete 
annelids,  Miss  Hyman  has  found  that  the  young  animals  show  a 
greater  susceptibility  to  cyanide  than  the  old.  The  young  in  these 
cases  arose  by  the  asexual  process  of  fission  and  not  from  fertilized 
eggs.  Various  species  of  entcmostracean  Crustacea  which  have 
been  examined  show  in  every  case  a  greater  susceptibility  in  the 
young  than  in  the  old  animals,  but  it  is  possible  that  differences  in 
size  may  be  a  factor  in  the  result  in  these  forms.  In  the  larvae  cf 
amphibia  the  susceptibility  is  greater  in  newly  hatched  animals 
than  in  later  stages. 

CONCLUSION 

The  uniform  results  obtained  from  widely  different  groups  show 
very  clearly  that  age  differences  in  susceptibility  to  cyanides  and 
other  narcotics  are  of  general  occurrence.  Moreover,  in  all  cases 
the  young  animals,  at  least  beyond  a  certain  stage,  show  the 
highest  susceptibility,  and  susceptibility  decreases  with  advancing 
development.  In  other  words,  the  rate  of  metabolism  is  highest 
in  the  young  animals  and  decreases  with  advancing  age.  This 
conclusion  is  in  full  agreement  with  what  we  know  of  the  physio- 
logical aspects  of  senescence  in  the  higher  animals,  and  it  forces 
us  to  the  further  conclusion  that  a  decrease  in  rate  of  metabolism  is 
at  least  very  generally  associated  with  growth  and  differentiation. 

REFERENCES 

CmLD,  CM. 

1913.     "The  Asexual  Cycle  in  Planar ia  velata  in  Relation  to  Senescence 
and  Rejuvenescence,"  Biol.  Bull.,  XXV. 

MiNOT,  C.  S. 

1908.     The  Problem  of  Age,  Growth  and  Death.     New  York. 


CHAPTER  V 

THE  RECONSTITUTIOX  OF  ISOLATED  PIECES  IX  RELATION  TO 
REJUVENESCENCE  IN  PLAXARIA  AND  OTHER  FORMS 

THE  RECOxsTiTUTioN  OF  PIECES  IN  Plauaria 

In  consequence  of  the  ability  of  isolated  pieces  cut  from  the  bod y 
to  develop  into  complete  individuals,  the  various  species  of  Plauaria 
have  served  to  a  very  large  extent  as  material  for  the  study  of 
*' form-regulation,"  ''regeneration,"  "restitution,"  as  the  changes 
which  occur  in  such  pieces  have  been  variously  called.  The  mor- 
phological and  histological  features  of  the  reconstitution  of  such 
pieces  into  new  wholes  have  been  repeatedly  discussed  by  various 
authors  and  for  various  species.  Since  the  essential  features  of 
the  process  do  not  differ  widely  in  the  different  species,  a  brief 
description  of  reconstitution  as  it  occurs  in  P.  dorotocephala  will 
serve  the  present  purpose.  The  reconstitution  of  such  a  piece  a> 
a  in  Fig.  14  is  shown  in  Figs.  15-17.  The  cut  surfaces  of  the  piec 
contract  after  its  isolation,  and  in  the  course  of  two  or  three  days 
outgrowths  of  new  embryonic  tissue  appear  on  these  surfaces, 
these  outgrowths  being  readily  distinguishable  from  other  parts  of 
the  piece  by  the  absence  of  the  dark-brown  pigment  characteristic 
of  the  species.  In  Fig.  15  and  following  figures  these  outgrowths 
of  new  tissue  are  marked  off  from  other  parts  by  lines  which  indicate 
the  boundaries  between  new  and  old  tissue.  During  the  ne.xt  two 
or  three  days  the  anterior  outgrowth  develops  into  a  head  with 
eyes,  cephalic  lobes  and,  as  the  section  shows,  a  new  cephalic 
ganglion,  and  the  posterior  outgrowth  develops  into  a  posterior 
end  (Fig.  16).  At  about  the  same  time  the  new  pharynx  becomes 
visible,  near  the  posterior  end  of  the  old  tissue  of  the  piece,  and  the 
intestinal  branches  present  in  the  piece  begin  the  changes  which 
end  in  the  formation  of  an  alimentary  tract  like  that  of  a  whole 
animal.  The  developing  animal  also  elongates  and  decreases  in 
width,  the  postpharyngeal  region  grows  at  the  expense  of  the  j^re- 
pharyngeal,  and  finally  an  individual  results  (Fig.  17)  which  is  in 
all  respects,  so  far  as  can  be  determined,  a  whole  animal  of  small 

103 


I04 


SENESCE^XE  AND  REJUVENESCENCE 


Figs.  14-17. — Reconstitution  of 
pieces  of  Planaria  dorotoccphala:  Fig. 
14,  body-outline  indicating  levels  of 
section;  Figs.  15-17,  three  stages  in 
the  reconstitution  of  an  isolated  piece. 


size.  Various  details  of  the  pro- 
cess differ  according  to  the  size  of 
the  piece,  the  level  of  the  body 
from  which  it  is  taken,  the  physio- 
logical condition  of  the  animal, 
and  the  environmental  conditions, 
and  a  limit  of  size  exists  which 
also  varies  with  all  these  factors; 
pieces  below  this  limit  of  size  do 
not  reproduce  complete  normal 
animals.  The  influence  of  these 
various  factors  is  evident  chiefly 
in  the  character  of  the  head, 
which  may  range  from  the  normal 
through  a  series  of  teratological 
forms  with  a  headless  condition 
as  the  extreme  term  of  the  series 
(Child,  '11&,  'lie;  see  also  Figs. 
20-23,  pp.  111-12).  In  other 
species  of  planarians  the  process 
of  reconstitution  is  in  general 
much  the  same,  but  with  differ- 
ences in  details  and  in  the  relation 
to  the  various  factors  mentioned 
above. 

The  process  of  reconstitution 
in  these  cases  differs  somewhat 
from  the  replacement  of  a  missing 
part  in  higher  animals.  The 
isolated  piece  of  Planaria  does  not 
replace  the  missing  parts  in  their 
original  condition  and  size,  but 
develops  merely  a  new  head  and 
posterior  end  and  then  undergoes 
an  extensive  reorganization  into 
a  new  individual  of  small  size, 
the  size  being  dependent  upon  the 


THE  RECONSTITUTION  OF  ISOLATED  PIECES  105 

size  of  the  isolated  piece.  In  the  course  of  the  process  some  parts 
of  the  piece  atrophy  and  disappear,  new  parts  arise  and  dilTcrcn- 
tiate,  and  a  large  amount  of  cell  division  and  growth  occur.  The 
piece  does  not,  in  many  cases  cannot,  feed  until  the  development  of 
the  new  individual  has  reached  a  certain  stage,  consequently  the 
energy  for  the  changes  which  occur  must  be  derived  from  the 
nutritive  reserves  and  the  tissues  of  the  piece  itself.  In  this  con- 
nection it  may  be  noted  that  the  volume  of  the  new  animal  is  al- 
ways considerably  less  than  that  of  the  piece  from  which  it  arose; 
in  other  words,  the  piece  undergoes  a  considerable  amount  of  reduc- 
tion in  producing  a  new  individual. 

The  development  of  the  new  animal  in  this  process  of  recon- 
stitution  is  not  fundamentally  different  from  embryonic  develop- 
ment (Child,  '12a,  '13) — it  merely  occurs  under  rather  different 
conditions;  nor  is  it  essentially  different  from  the  process  of  agamic 
reproduction  in  nature;  it  is,  in  short,  an  experimental  reproduction. 
Moreover,  the  new  animal  thus  produced  resembles  a  young  ani- 
mal in  its  morphological  features  and  is  capable,  when  fed,  of  growth 
and  development,  in  fact,  of  going  through  all  stages  of  the  hfe 
history  beyond  that  which  it  apparently  represents.  All  these 
facts  raise  the  question  whether  such  an  animal  is  or  may  be  younger 
physiologically  as  well  as  morphologically  than  the  animal  from 
which  the  piece  was  taken.  This  question  is  considered  in  the 
following  section. 

CHANGES   IN   SUSCEPTIBILITY   DURING   THE   RECONSTITUTION 

OF   PIECES 

An  extensive  investigation  of  the  changes  during  reconstitution 
in  the  susceptibility  of  isolated  pieces  to  cyanide  has  been  made  by 
the  direct  susceptibility  method.  It  should  be  borne  in  mind  that 
changes  in  susceptibility  as  indicated  by  this  method  indicate 
change  in  the  same  direction  of  rate  of  metabolism.  The  results 
of  these  experiments  are  given  here  only  in  general  terms.  The 
complete  data  have  appeared  elsewhere  (Child,  '14^1). 

The  first  change  follows  immediately  upon  the  act  of  isolation. 
The  susceptibility  of  the  piece  immediately  after  isolation  is  greater, 
i.e.,  its  rate  of  metabolism  is  higher,  than  that  of  the  same  region 


io6  SENESCENCE  AND  REJUVENESCENCE 

of  the  body  in  uninjured  animals  which  are  as  nearly  as  possible 
in  the  same  physiological  condition  as  that  from  which  the  piece 
was  taken. 

This  is  of  course  to  be  expected,  for  the  operation  of  cutting 
the  piece  out  of  the  body  undoubtedly  stimulates  it  and  so  increases 
its  rate  of  metabohsm,  and  the  presence  of  the  wounds  at  the  two 
ends  of  the  piece  undoubtedly  serves  to  continue  this  stimulation. 
It  is  an  interesting  fact  that  short  pieces  show  a  greater  increase 
in  rate  of  metabolism  than  long,  as  the  result  of  section.  This 
again  is  only  to  be  expected,  for  the  nearer  the  cut  is  to  a  given 
region  of  the  body,  the  more  directly  the  nervous  structures  inner- 
vating that  region  are  affected  by  it.  When  the  piece  includes  a 
half  or  a  third  of  the  body,  the  stimulation  following  section,  as 
indicated  by  an  increase  in  rate  in  the  piece  as  a  whole,  is  slight, 
but  the  degree  of  stimulation  increases  as  the  length  of  the  piece 
decreases,  and  in  short  pieces,  including  one-eighth  or  less  of  the 
body-length,  the  increase  in  rate  is  great. 

But  this  increase  in  rate  following  section  is  only  temporary, 
as  we  should  expect,  if  it  is  due  to  the  stimulation  resulting  from 
section.  The  rate  of  metabolism  in  the  isolated  piece,  as  measured 
by  its  susceptibihty  to  cyanide,  decreases  during  the  first  few  hours 
after  section.  In  long  pieces,  including  a  half  or  a  third  of  the 
body-length,  the  rate  falls  to  about  the  same  level  as  that  in  the 
corresponding  region  of  the  parent  body,  or  somewhat  lower.  But 
in  shorter  pieces  the  rate  does  not  fall  as  low,  and  in  very  short 
pieces  it  may  remain  considerably  higher  than  in  the  same  region 
of  the  uninjured  animal,  probably  because  in  such  cases  the  wound 
stimulus  involves  the  whole  piece  to  a  greater  or  less  extent.  The 
decrease  in  metaboUc  rate  following  the  increase  after  isolation  is 
evidently  due  to  the  gradual  recovery  from  the  condition  of  excita- 
tion following  the  act  of  section. 

But  this  condition,  like  the  initial  condition  of  stimulation,  is 
only  temporary  in  cases  where  the  piece  undergoes  reconstitution. 
Within  three  or  four  days  after  section  the  processes  of  reconstitu- 
tion are  well  under  way,  and  they  are  accompanied  by  an  increase 
in  susceptibility,  i.e.,  an  increase  in  rate  of  metabolism  in  the  pieces. 
This  continues  as  reconstitution  goes  on,  and  when  the  develop- 


THE  RECONSTITUTION  OF  ISOLATED  PIECES  107 

ment  of  the  new  animal  from  the  piece  is  completed,  the  suscepti- 
biUty  is  greater  than  that  in  the  corresponding  region  of  the  parent 
animal.  This  means  that  during  reconstitution  the  rate  of  metab- 
olism increases  until  it  is  higher  than  before  section.  This  increase 
in  rate  is  not  the  result  of  a  stimulation  which  soon  disappears,  but 
is  connected  with  the  process  of  reconstitution  and  is  relatively 
permanent.  The  rate  after  reconstitution  is  the  rate  characteristic 
of  a  physiologically  young  animal,  and  it  undergoes  a  gradual 
decrease  as  the  animal  grows  and  becomes  physiologically  older. 
Here  also  size  is  a  factor  in  the  result:  the  smaller  the  piece  which 
undergoes  reconstitution  into  a  new  whole,  the  greater  the  increase 
in  rate  of  reaction  during  reconstitution.  This  increase  in  meta- 
bolic activity  during  reconstitution  was  first  discovered  by  means 
of  the  acclimation  method  with  alcohol  as  a  reagent  (Child,  '11). 
In  these  earlier  experiments  a  marked  increase  in  rate  was  found 
in  small  pieces,  but  in  very  large  pieces  a  decrease  in  rate  apparently 
occurred.  As  a  matter  of  fact,  the  rate  does  not  decrease  in  large 
pieces  during  reconstitution,  but  increases  slightly.  My  error  on 
this  point  was  due  to  failure  to  keep  the  normal  animals  under  the 
same  conditions  as  the  experimental  pieces.  In  the  case  of  the 
large  pieces  the  effect  of  the  conditions  more  than  compensated  the 
slight  increase  in  rate  due  to  reconstitution,  but  in  the  small  pieces, 
where  the  increase  was  much  greater,  it  appeared  in  spite  of  the 
external  conditions. 

More  recent  and  extended  investigation  by  the  direct  method 
with  cyanide  as  reagent  has  demonstrated  beyond  a  doubt  that 
reconstitution  is  accompanied  by  an  increase  in  rate,  the  amount 
of  increase  varying  with  the  size  of  the  piece,  the  amount  of  reconsti- 
tutional  change,  and  various  other  factors. 

The  partial  record  of  one  series  of  experiments  will  serve  to 
show  both  the  increase  in  susceptibility,  i.e.,  of  rate  of  metabolism 
resulting  from  reconstitution,  and  the  relation  between  the  amount 
of  increase  and  the  size  of  the  piece.  In  this  experiment  large, 
physiologically  old  worms  eighteen  to  twenty  millimeters  in  length 
constituted  the  material.  From  a  part  of  these  worms  pieces  in- 
cluding the  region  ac  in  Fig.  18,  from  another  part  pieces  including 
the  region  ah,  i.e.,  just  half  the  length  of  the  preceding  lot,  were 


io8 


SENESCENCE  AND  REJUVENESCENCE 


U 


cut.  These  two  lots  of  pieces  were  allowed 
to  develop  into  new  animals.  A  third  part 
of  the  stock  consisting  of  uninjured  worms 
was  kept  under  the  same  conditions  as  a 
control  and  since  the  pieces  do  not  feed 
during  the  process  of  reconstitution,  this 
third  lot  was  not  fed.  During  the  recon- 
stitution of  the  pieces  several  comparative 
tests  were  made  of  their  susceptibihty,  and 
of  that  of  the  uninjured  animals,  to 
cyanide.  The  results  of  one  of  these  tests 
made  sixteen  days  after  the  pieces  were 
cut  from  the  parent  bodies  is  given  in 
Fig.  19.  Both  the  pieces  and  the  whole 
animals  had  been  without  food  during  this 
time,  but  the  effects  of  sixteen  days' 
starvation  are  not  very  great  as  regards 
susceptibility.  During  these  sixteen  days 
the  pieces  had  become  fully  developed 
animals,  the  longer  being  seven  to  eight 
milHmeters,  the  shorter,  five  miUimeters  in 
length.  In  Fig.  19  the  curve  ab  shows  the 
susceptibihty  of  ten  animals  developed 
from  the  shorter  pieces,  the  curve  cd  the 
susceptibihty  of  ten  animals  from  the 
longer  pieces,  and  the  curve  ef  the  suscepti- 
bility of  uninjured  animals  the  same  size 
as  those  from  which  the  pieces  were  taken. 
It  is  evident  at  once  from  the  figure  that 
the  susceptibihty  of  the  pieces  which  have 
undergone  reconstitution  to  whole  animals 
is  very  considerably  greater  than  that  of 
the  uninjured  animals  like  those  from 
which  these  pieces  came,  and  that  further 
the  susceptibihty  of  the  animals  which 
develop  from  the  shorter  pieces  is  greater  than  that  of  those  from 
the  longer.     The  results  of  all  other  similar  tests  of  susceptibihty 


Fig.  18. — Body-outline 
of  Planar i a  dorotocephala, 
indicating  levels  of  section. 


THE  RECONSTITUTION  OF  ISOLATED  PIECES 


109 


have  been  essentially  the  same.  When  the  pieces  are  very  large 
and  include  a  considerable  portion  of  the  body,  the  increase  in 
susceptibility  is  slight  or  inappreciable,  but  with  decrease  in  size  of 
piece  increase  in  susceptibility  becomes  greater,  provided  the  pieces 
are  not  so  small  that  they  fail  to  undergo  complete  reconstitution. 
Recalling  the  age  differences  in  susceptibility  shown  in  the 
preceding  chapter  to  exist,  it  is  evident  that  the  animals  resulting 
from  the  reconstitution  of  pieces  are,  at  least  as  regards  their 

Stages  I  ace 


Hours  2345678 

Fig.  19. — Susceptibility  of  Planaria  dorolocepkala  to  KCNo.ooi  mol.:   ab,  short 
pieces;  cd,  long  pieces;   ef,  uninjured  worms  like  those  from  which  pieces  were  taken. 

susceptibility,  younger  than  the  animals  from  which  the  pieces  were 
taken.  Apparently  the  process  of  reconstitution  brings  about  in 
some  way  a  greater  or  less  degree  of  rejuvenescence  as  regards  the 
susceptibility  to  cyanide,  i.e.,  the  rate  of  metabolism.  The  smaller 
the  piece,  the  greater  the  amount  of  reorganization  in  the  forma- 
tion of  a  whole  animal  and  the  greater  the  degree  of  rejuvenescence. 
In  this  connection  it  is  of  interest  to  note  that  the  new  tissue 
formed  at  the  cut  ends  of  the  piece  is  for  a  considerable  time  after 
its  formation  distinctly  more  susceptible  to  cyanide,  i.e..  younger 


no  SENESCENCE  AND  REJUVENESCENCE 

physiologically,  than  the  old  tissues  of  the  rest  of  the  piece.  As 
the  new  tissue  differentiates,  however,  this  difference  in  suscepti- 
bihty  between  it  and  the  old  parts  gradually  disappears,  for  the 
new  tissue  gradually  grows  old  and  its  rate  of  metabolism  decreases, 
while  the  old  tissue  gradually  undergoes  reconstitutional  changes 
which  involve  the  atrophy  and  disappearance  of  some  parts  and  the 
formation  of  others  by  cell  division  and  growth,  and  besides  this 
the  tissues  of  the  piece,  particularly  the  old  tissues  with  their  lower 
rate  of  metabohsm,  are  being  used  up  as  a  source  of  nutrition  for 
the  developing  organism.  In  other  words,  the  new  embryonic 
tissue  formed  at  the  cut  surfaces  gradually  becomes  old  after  its 
formation,  while  other  parts  of  the  piece  gradually  become  young 
by  reduction  and  reorganization,  until  a  dynamic  equihbrium  is 
estabhshed  in  the  rate  of  metabolism  in  the  different  parts,  after 
which  the  animal,  if  fed,  undergoes  senescence  as  a  whole. 

With  various  other  organisms  which  show  a  high  capacity  for 
reconstitution  similar  results  have  been  obtained.  In  various  other 
species  of  flatworms,  so  far  as  tested,  in  Hydra  and  in  the  hydroid 
Corymorpha,  the  animals  resulting  from  the  reconstitution  of 
pieces  show  a  higher  rate  of  metabolism  than  the  animals  from  which 
the  pieces  were  taken.  Miss  Hyman  has  found  that  this  is  also 
true  for  animals  developed  from  pieces  of  Lumbriculus  and  other 
fresh-water  oligochete  annelids. 

Animals  produced  in  this  way  are  also  younger  in  other  respects 
than  those  from  which  the  pieces  came.  They  grow  more  rapidly 
and  are  capable  of  repeating  the  developmental  history  from  the 
stage  which  they  represent  onward.  There  can  be  no  doubt  that 
the  process  of  reconstitution  brings  about  in  some  way  a  greater 
or  less  degree  of  rejuvenescence  in  these  relatively  simple  animals, 
and  that  the  degree  of  rejuvenescence  is  in  general  proportional  to 
the  degree  of  reorganization  in  the  process  of  reconstitution  of  the 
piece  into  a  whole. 

THE    INCREASE    IN    SUSCEPTIBILITY    IN    RELATION    TO    THE    DEGREE 

OF  RECONSTITUTION 

The  reconstitutional  capacity  of  pieces  of  Planaria  dorotocephala, 
as  of  other  species,  is  limited.     Pieces  below  a  certain  size  limit, 


THE  RECOXSTITUTIOX  OF  ISOLATED  riKCES  1 1  r 

which  varies  with  the  condition  of  the  animal,  with  the  le\el  of  the 
body  from  which  the  piece  is  taken,  and  with  various  external 
factors  which  influence  the  rate  of  metabohsm,  do  not  produce 
complete  normal  animals,  although  they  may  undergo  a  greater 
or  less  degree  of  reconstitution  and  approach  more  or  less  closely 
to  the  normal  form.  Such  pieces  show  all  gradations  between  the 
normal  animal  at  one  extreme  and  a  completely  headless  form  at 
the  other  (Child,  'iib,  'iic,  '12b).  It  has  been  found  convenient 
to  distinguish  in  this  graded  series  of  forms  five  different  types,  as 
follows: 

Normal. — The  head  is  like  that  of  animals  found  in  nature  with 
two  completely  separated  eyes  and  cephalic  lobes  at  lateral  margins 
(Fig.  17). 


::m)     (M)     en: 


Fig.  20. — Various  degrees  of  teratophthalmia  in  Planaria  dorolocephala 

Teratophthalmic. — The  head  is  of  the  usual  form,  but  the  eye 
spots  show  differences  in  size,  asymmetry  in  position,  approach  to 
the  median  line,  or  various  degrees  of  fusion.  Some  of  the  eye 
forms  are  shown  in  Fig.  20.  In  all  teratophthalmic  animals  the 
cephalic  ganglia  show  various  degrees  of  fusion  or  asymmetry,  the 
condition  of  the  eyes  being  to  a  considerable  extent  indicative  of 
that  of  the  ganglia. 

Teratomorphic. — Here  the  preocular  region  of  the  head  fails  to 
attain  its  full  size  or  does  not  appear  at  all.  Consequently  the 
cephalic  lobes  arise  on  the  anterior  margin  of  the  head  as  in 
Fig.  21  ^,  or  in  extreme  cases  are  fused  together  in  the  median  line 
at  the  front  of  the  head  (Fig.  21  B). 


112 


SENESCENCE  AND  REJUVENESCENCE 


Anophthalmic. — The  anterior  outgrowth  of  new  tissue  is  vari- 
able in  form  and  without  eyes,  but  contains  a  small,  single,  gangU- 
onic  mass,  i.e.,  it  is  a  rudimentary  head  (Figs.  22  A,  22  B). 

Headless.— The  anterior  outgrowth  merely  fills  in  the  contracted 
cut  surface  and  does  not  extend  beyond  the  contours  of  the  margin; 
the  posterior  outgrowth,  however,  is  usually  even  longer  than  in 
other  pieces,  but  its  differentiation  proceeds  very  slowly  and  is 
never  completed  as  long  as  it  is  attached  to  the  headless  piece 

(Fig.  23). 

The  difference  between  the  extremes  of  this  series,  the  normal 
and  headless  forms,  in  the  degree  of  reorganization  is  very  great, 


21 


Figs.  21-23. — Different  degrees  of  reconstitution  in  Planaria  doroiocephala: 
Fig.  21  A,  B,  teratomorphic  forms;  Fig.  22  A,  B,  anophthalmic  forms;  Fig.  23, 
headless  form. 

particularly  in  pieces  from  the  postoral  region  (eg.,  a,  Fig.  24).  In 
the  development  of  a  normal  animal  the  anterior  half  or  more  of 
such  a  piece  undergoes  extensive  changes  in  giving  rise  to  a  pharyn- 
geal and  prepharyngeal  region,  and  outgrowths  of  new  tissue  appear 
at  both  ends.  In  the  piece  from  this  region  which  remains  headless 
no  prepharyngeal  or  pharyngeal  region  arises,  and  changes  are 
Hmited  to  the  longer  outgrowth  at  the  posterior  end  and  the  smaller 
amount  of  new  tissue  at  the  anterior  end. 

In  the  teratophthalmic,  teratomorphic,  and  anophthalmic  forms 
the  degree  of  reconstitutional  change  ranges  from  a  little  less  than 
in  the  normal  animal  to  somewhat  more  than  in  the  headless  form. 
Moreover  the  degree  of  reconstitution  decreases  somewhat  as  the 


THE  RECONSTITUTION  OF  ISOLATED  PIECES 


113 


\J 


character  of  the  head  departs  from  normal. 
In  pieces  of  the  same  length  and  from  the 
same  region  the  size  of  the  head  and  the 
length  of  the  pharyngeal  and  prepharyn- 
geal  region  are  less  in  teratophthalmic  and 
teratomorphic  than  in  normal  animals  and 
less  in  anophthalmic  than  in  teratomorphic 
or  teratophthalmic  forms.  Between  the 
teratophthalmic  and  teratomorphic  forms 
the  differences  in  this  respect  are  not  very 
great  except  when  opposite  extremes  of  the 
two  t>pes  are  compared. 

That  the  production  of  a  normal  or 
nearly  normal  animal  from  a  piece  requires 
more  energy  than  the  production  of  a  head- 
less form  is  indicated  by  the  fact  that  a 
much  greater  amount  of  reduction  occurs 
in  the  former  than  in  the  latter  case. 
Moreover,  in  a  given  lot  of  pieces  it  is 
possible  by  means  of  external  conditions 
such  as  temperature,  low  concentrations  of 
narcotics,  etc.,  whose  effect  is  primarily 
quantitative  rather  than  qualitative,  to 
determine  experimentally  within  wide 
limits  which  of  the  five  forms  shall  be  pro- 
duced (Child,  '116,  '126).  Experiments  of 
this  kind  have  demonstrated  that  all  four 
forms-  from  the  teratophthalmic  to  the 
headless  are  what  might  be  called  sub- 
normal, i.e.,  they  are  due  to  various  degrees 
of  retardation  or  inhibition  of  the  dynamic 
processes  (Child,  'iib,  '14a,  '14b).  And, 
finally,  after  their  development  is  com- 
pleted, the  normal  head  shows  in  general 
a  higher  susceptibility  than  the  teratoph- 
thalmic and  teratomorphic,  and  these  a  higher  susceptibility  than 
the  anophthalmic. 


a 


Fig.  24. — Body-outline 
of  Pliiihiria  dorotoii'Phiihi, 
indicating  levels  of  section. 


114  SENESCENCE  AND  REJUVENESCENCE 

It  is  evident,  then,  from  all  points  of  view,  that  these  different 
forms  represent  different  degrees  of  reconstitution.  If  the  degree 
of  rejuvenescence,  as  indicated  by  the  increase  in  susceptibility, 
is  associated  with  the  degree  of  reconstitution,  then  these  different 
forms,  when  produced  under  comparable  conditions,  should  show 
the  highest  susceptibility  in  the  normal,  the  lowest  in  the  headless 
animals,  with  intermediate  conditions  in  the  intermediate  forms. 
The  following  experiment  shows  to  what  extent  this  is  the  case. 

The  stock  for  the  experiment  consisted  of  a  hundred  or  more 
pieces  like  a  in  Fig.  24,  cut  from  animals  of  equal  size  and  similar 
physiological  condition  and  allowed  to  undergo  reconstitution 
under  uniform  external  conditions.  Even  under  such  conditions 
pieces  of  this  size  and  from  this  region  may  produce  anything  from 
normal  to  headless  forms,  although  the  great  majority  are  headless 
or  anophthalmic. 

Eleven  days  after  section  reconstitution  was  practically  com- 
plete, and  the  susceptibilities  of  lots  of  ten  each  of  the  different 
forms  and  at  the  same  time  of  a  lot  of  ten  intact  worms  like  those 
from  which  the  pieces  had  been  taken  were  determined.  The 
control  animals  had  been  kept  under  the  same  conditions  as  the 
pieces,  and,  like  them,  without  food  during  the  eleven  days  of  the 
experiment,  and  the  difference  in  susceptibility  between  the  pieces 
and  these  whole  animals  should  show  how  much  rejuvenescence 
had  occurred  in  connection  with  reconstitution. 

The  results  appear  in  the  susceptibility  curves  of  Fig.  25.  The 
curve  of  the  whole  animal  is  drawn  in  an  unbroken  line,  that  of  the 
normal  animals  developed  from  pieces  in  short  dashes,  that  of 
the  teratophthalmic  forms  in  long  dashes,  that  of  the  anoph- 
thalmic forms  in  alternate  long  and  short  dashes,  and  that  of  head- 
less forms  in  dots.  The  susceptibility  is  highest  in  the  normal 
animals  developed  from  pieces,  slightly  lower  in  the  teratophthalmic 
forms,  considerably  lower  in  the  anophthalmic  forms,  and  again 
still  lower  in  the  headless  forms.  In  all  except  the  headless  forms 
the  susceptibility  is  higher  than  in  the  whole  animals,  i.e.,  it  has 
increased  during  reconstitution. 

The  susceptibility  curve  of  the  headless  pieces  shows  an  inter- 
esting relation  to  that  of  the  whole  animals.     In  earlier  stages  the 


THE  RECONSTITUTION  OF  ISOLATED  PIECES 


1 1 


susceptibility  of  the  headless  forms  falls  below  that  of  the  whole 
animals,  but  later  rises  considerably  above  it.  This  is  simply 
an  expression  of  the  fact  that  there  is  no  part  of  the  headless  piece 
which  has  as  high  a  rate  of  metabolism  as  the  head-region  of  the 
whole  animal,  but  that  the  rate  in  the  headless  piece  is  considerably 
higher  than  that  of  the  regions  of  lowest  rate  in  the  whole  animal. 
It  is  also  evident  from  Fig.  25  that  the  difference  between  normal 
Stages 


Hours  1234567 

Fig.  25. — Susceptibility  of  Planaria  dorotocephala  to  KCX  o.ooi  mol.  after 
different  degrees  of  reconstitution :  unbroken  line,  uninjured  animals  like  those  from 
which  pieces  were  taken;  short  dashes,  normal  forms  after  reconstitution;  long 
dashes,  teratophthalmic  forms;  alternate  long  and  short  dashes,  anophthalmic  forms; 
dots,  headless  forms. 

and  teratophthalmic  forms  is  slight  and  much  less  than  that  between 
teratophthalmic  and  anophthalmic  forms. 

These  curves  are  a  graphic  presentation  in  dynamic  terms  of 
the  degree  of  rejuvenescence  in  its  relation  to  the  degree  of  recon- 
stitution. Similar  tests  of  the  susceptibility  of  the  ditTerent 
reconstitutional  forms  have  been  made  repeatedly  with  pieces  of 
different  size  and  from  different  regions  of  the  body  and  always 
with  essentiallv  the  same  result. 


ii6 


SENESCENCE  AND  REJITV^ENESCENCE 


(»)  (D 


a 


THE   SUSCEPTIBILITY  OF  ANIMALS  RESULTING  FROM  EXPERIMENTAL 
REPRODUCTION  AND  SEXUALLY  PRODUCED  ANIMALS 

The  belief  that  the  germ  cell  is  the  source  of  youth  and  that  the 
old  organism  cannot  become  young  has  been  so  widely  current 

among  biologists  that  it  is  of  some  interest  to 
determine  whether  the  physiological  condition 
of  the  animal  resulting  from  reconstitution 
approaches  that  of  the  sexually  produced  young 
animal.  Planaria  dorotocephala  is  not  available 
for  such  experiments,  since  it  does  not  repro- 
duce sexually  under  ordinary  conditions,  con- 
sequently another  species,  P.  maculata,  has  been 
used  in  which  the  young  produced  from  eggs 
can  readily  be  obtained. 

In  experiments  of  this  kind  pieces  were  cut 
from  old,  sexually  mature  animals  and  allowed 
to  undergo  reconstitution;  after  reconstitution 
their  susceptibihty  was  compared  with  that  of 
sexually  produced  young  of  the  same  size.  In 
the  particular  experiment  of  which  the  results 
are  given  in  Fig.  27  below,  two  lots  of  pieces 
(a  and  h,  Fig.  26)  were  cut  from  old,  sexually 
mature  worms  twelve  millimeters  in  length. 
These  pieces  were  left  for  ten  days  under  uni- 
form conditions,  at  the  end  of  which  time  they 
had  become  normal  animals  five  to  six  milli- 
meters long.  They  were  then  fed,  and  two  days 
later  their  susceptibility  was  compared  both 
with  that  of  old,  sexually  mature  worms  like 
those  from  which  the  pieces  were  taken  and  also 
with  that  of  young,  growing  worms  five  to  six 
millimeters  long,  which  had  been  hatched  from 
eggs  in  the  laboratory. 

Fig.  27  shows  the  susceptibihties  to  KCN 
o.ooi  mol.  of  ten  old,  sexually  mature  worms 
{cd),  ten  young,  growing  worms  hatched  from  eggs  {ah,  long 
dashes),    ten    animals    developed    from    the    a-pieces    {ah,    short 


Fig.  26. — Body- 
outline  of  Planaria 
maculata,  indicating 
levels  of  section. 


THE  RECONSTITUTION  OF  ISOLATED  PIECES 


117 


dashes),  and  ten  animals  developed  from  the  6-pieces  (ab,  unbroken 
line).  The  figure  shows  that  the  susceptibility  of  animals  resulting 
from  the  reconstitution  of  pieces  is  practically  the  same  as  that  of 
the  young,  growing,  sexually  produced  animals  of  the  same  size 
and  much  greater  than  that  of  the  old,  sexually  mature  animals. 
In  other  words,  the  animals  resulting  from  experimental  repro- 
duction possess  about  the 
same  rate  of  metabolism  as  Stages  .. 
sexually  produced  growing 
animals  of  the  same  size,  and 
a  much  higher  rate  than  the 
animals  from  which  the  pieces 
were  taken.  The  process  of 
reconstitution  has  made  the 
experimentally  produced  ani- 
mals as  young  as  the  sexually 
produced  animals  of  the  same 
size. 

It  is  of  interest,  however, 
to  note  that  the  ^-pieces  from 
the  posterior  end  of  the  ani- 
mal (Fig.  26)  show  a  some- 
what greater  susceptibility 
than  the  a-pieces  from  the 
anterior  body  region.  This 
difference  in  susceptibility 
corresponds  to  a  real  differ- 
ence in  the  process  of  recon- 
stitution in  pieces  from  these 
two  regions.  In  the  recon- 
stitution of  the  6-pieces  there  is  less  outgrowth  of  new  tissue 
and  more  reorganization  of  the  old  than  in  the  j-picces,  so  that 
the  old  tissue  becomes  somewhat  younger  in  the  former  than 
in  the  latter;  consequently,  as  the  new  tissue  becomes  older  and 
the  old  tissue  younger,  they  finally  attain  the  same  physiological 
age  at  a  stage  somewhat  younger  in  the  i-pieces  than  in  the  a- 
pieces.     Slight  differences  of  this  kind  are  characteristic  of  pieces 


Hours  1234 

Fig.  27. — Susceptibility  of  P/iiHcir/j  mcicii- 
lala  to  KCX  o.ooi  mol.:  ab,  long  dashes, 
sexually  produced  young;  ab,  short  dashes 
and  unbroken  line,  animals  resulting  from 
reconstitution  of  pieces;  cd,  animals  like 
those   from  which  the  pieces  were  taken. 


Ii8  SENESCENCE  AND  REJUVENESCENCE 

from  different  body  levels  and  are  correlated  with  differences  in 
the  process  of  reconstitution. 

If  pieces  smaller  than  these  are  taken,  the  increase  in  suscepti- 
bihty  is  greater  and  the  animals  attain  the  condition  of  still  younger 
sexually  produced  forms.  Evidently  these  experimental  repro- 
ductions, while  they  do  not  carry  the  organism  back  to  the 
beginning  of  development,  do  carry  it  back  to  the  physiological 
condition  characteristic  of  the  sexually  produced,  growing  animal 
of  the  same  size.  Experimental  reproduction  is  apparently  in  this 
species  just  as  efficient  a  means  of  producing  physiologically  young 
animals  as  sexual  reproduction. 

REPEATED  RECONSTITUTION 

It  has  been  shown  in  preceding  sections  that  the  animals 
produced  by  reconstitution  are  physiologically  younger  than  the 
animals  from  which  the  pieces  are  taken,  and  moreover  that  they 
are  about  as  young  as  sexually  produced  animals  of  the  same  size. 
If  this  is  the  case,  it  should  be  possible  to  breed  animals  indefinitely 
by  means  of  this  process  of  experimental  reproduction.  On  the 
other  hand,  the  animal  rejuvenated  by  reconstitution  may  differ  in 
some  way  from  the  sexually  produced  animal,  but  so  slightly  that 
the  difference  does  not  become  apparent  in  a  single  generation, 
but  requires  several  or  many  generations  of  breeding  by  experi- 
mental reproduction  to  become  distinguishable.  Thus  far  two 
attempts  at  reconstitutional  breeding  have  been  made,  both  of 
which  were  terminated  by  accident,  but  one  of  them  continued 
long  enough  to  throw  at  least  some  light  on  the  question. 

The  breeding  stock  for  these  experiments  was  obtained  as 
follows:  Large  individuals  of  the  same  size,  which  had  been  kept 
under  uniform  conditions,  were  selected,  and  from  each  of  these 
a  piece  of  a  certain  size  and  from  a  certain  region  of  the  body  was 
taken.  These  pieces  were  allowed  to  undergo  reconstitution  and 
after  this  was  completed  were  fed  until  they  attained  approxi- 
mately the  original  size.  Then  from  each  a  piece,  including  the 
same  region  of  the  body,  was  taken;  these  were  again  allowed  to 
develop,  were  fed,  and  so  on.  In  one  of  these  breeding  experiments 
the  piece  used  in  each  generation  was  the  anterior  fifth  of  the  body, 


THE  RECONSTITUTION  OF  ISOLATED  PIECES  119 

including  the  old  head.  In  such  pieces  the  old  head  remains  from 
one  generation  to  another  and  new  tissue  appears  only  at  the 
posterior  end;  consequently  the  amount  of  reorganization  is  less 
than  in  pieces  which  form  a  new  head  or  in  pieces  from  the  posterior 
region  of  the  body.  Moreover,  the  head-region  is  less  capable  of 
reorganization  than  other  parts  of  the  body.  If  a  progressive 
senescence  occurs  from  generation  to  generation  in  spite  of  recon- 
stitution  in  each  generation,  it  should  become  more  distinct  or 
appear  earher  in  such  pieces  than  in  those  where  the  reconstitu- 
tional  changes  are  more  extensive. 

In  the  course  of  a  year  and  a  half  the  animals  passed  through 
thirteen  experimental  generations  without  any  indications  of 
senescence  or  depression  of  any  sort.  During  the  growth  of  the 
thirteenth  generation,  however,  most  of  the  stock  was  killed  by 
high  temperature  and  the  remaining  animals  never  regained  good 
condition,  but  died  in  the  course  of  the  next  few  generations.  The 
worms  that  remained  alive  in  each  generation  grew  more  or  less 
normally,  and  the  breeding  was  continued  with  these.  In  the  six- 
teenth generation  only  eight  worms  remained  alive,  and  in  order  to 
determine  whether  more  extensive  reconstitutional  change  would 
bring  the  animals  back  to  their  original  condition,  the  old  heads 
were  removed  and  each  animal  was  cut  into  several  pieces.  Some  of 
these  pieces  produced  complete  animals,  but  deaths  continued  to 
occur  among  these,  and  some  of  the  pieces  died  without  reconstitu- 
tion.  The  living  animals  were  again  cut  into  pieces  after  growth, 
and  this  was  repeated  to  the  nineteenth  generation  in  which  the 
last  of  the  stock  died  without  recovery. 

In  another  stock  pieces  from  the  middle  region  of  the  body  were 
used  for  each  generation.  In  the  fifth  generation  this  stock  was 
subjected  to  high  temperature  at  the  same  time  as  the  preceding, 
and  most  of  the  animals  died.  Those  that  remained  alive  gradually 
died  during  the  following  generations,  until  in  the  tenth  genera- 
tion all  were  dead. 

The  results  of  these  two  breeding  experiments  are  of  value  only 
as  far  as  they  go.  The  first  does  show,  however,  that  the  animals 
can  be  bred  by  experimental  reproduction  without  loss  of  vigor 
for    at    least    thirteen   generations,    even   when    the   old   head   is 


I20  SENESCENCE  AND  REJUVENESCENCE 

continuously  present.  The  first  stock  was  subjected  to  high 
temperature  in  the  thirteenth  generation,  the  second  in  the  fifth 
generation,  but  in  both  the  result  was  the  same,  in  that  most  of 
the  stock  was  killed  and  the  survivors  failed  to  recover  after  several 
months.  There  can  be  little  doubt  that  the  high  temperature 
rather  than  the  physiological  condition  of  the  animals  was  respon- 
sible in  one  way  or  another  for  the  death  of  both  stocks. 

As  a  matter  of  fact,  however,  the  question  which  these  experi- 
ments attempted  to  answer  is  answered  by  reproduction  in  nature 
in  Planaria  dorotocephala  and  P.  velata.  It  will  be  shown  in  the 
following  chapter  that  the  process  of  agamic  reproduction  in  these 
forms  is  not  essentially  different  in  any  way  from  the  process 
of  reconstitution  of  pieces,  and  this  is  the  only  method  of  reproduc- 
tion which  has  been  observed  in  these  two  species  under  natural 
conditions. 

The  results  obtained  by  another  method  of  experiment  are  of 
interest  in  this  connection.  This  is  essentially  breeding  by  experi- 
mental reproduction  without  food.  Pieces  from  large,  old  animals 
are  allowed  to  undergo  reconstitution;  then,  without  feeding,  pieces 
are  taken  from  these  animals,  and  so  on.  Here  of  course  each 
generation  is  smaller  than  the  preceding,  and  the  experiment  is 
finally  brought  to  an  end  by  the  advancing  starvation  of  the  animals 
and  the  failure  of  the  minute  pieces  to  undergo  reconstitution.  But 
susceptibility  tests  show  that  the  susceptibility  increases  with  such 
reconstitutions,  and  in  Planaria  maculata,  where  sexually  produced 
animals  are  available  for  comparison,  the  animals  after  a  few  genera- 
tions of  reconstitution  without  food  show  a  susceptibility  equal  to 
that  of  animals  just  hatched  from  the  egg  capsule.  Their  rate  of 
metabolism  has  increased  in  consequence  of  the  successive  recon- 
stitutions and  the  absence  of  food  until  it  equals  that  of  very 
young  sexually  produced  animals.  If  fed  after  such  a  series  of 
reconstitutions,  they  grow  and  are  indistinguishable  from  the 
animals  hatched  from  eggs. 

In  short,  by  successive  reconstitutions  alternating  with  feeding 
and  growth,  the  animals  may  be  brought  back  to  essentially  the 
same  stage  in  the  age  cycle  in  each  successive  generation,  and  by 
successive  reconstitutions  without  feeding  and  growth  they  may  be 


THE  RECONSTITUTION  OF  ISOLATED  PIECES  121 

made   progressively   younger   physiologically   in   each   successive 
generation,  until  further  reconstitution  becomes  impossible. 

REFERENCES 
Child,  CM. 

1911a.  "A  Study  of  Senescence  and  Rejuvenescence  Based  on  Experi- 
ments with  Planarians,"  Arch.  f.  Entwickelungsmech.,  XXXI. 

191 16.  "Experimental  Control  of  Morphogenesis  in  the  Regulation  of 
Planaria;'  Biol.  Bull.,  XX. 

1911C.  "Studies  on  the  Dynamics  of  Morphogenesis  and  Inheritance  in 
Experimental  Reproduction:  I,  The  Axial  Gradient  in  Planaria 
dorotocephala  as  a  Limiting  Factor  in  Regulation,"  Jour,  of  Exp. 
Zool.,  X. 

1912a.  "The  Process  of  Reproduction  in  Organisms,"  Biol.  Bull.,  XXIII. 

1912&.  "Studies  on  the  Dynamics,  etc.:  IV,  Certain  Dynamic  Factors  in 
the  Regulatory  Morphogenesis  of  Planaria  dorotocephala  in  Rela- 
tion to  the  Axial  Gradient,"  Jour,  of  Exp.  Zool.,  XIII. 

1913.  "Certain  Dynamic  Factors  in  Experimental  Reproduction  and 
Their  Significance  for  the  Problems  of  Reproduction  and  Develop- 
ment," Arch.  J.  Entwickelungsmech.,  XXXV. 

1914a.  "Studies  on  the  Dynamics,  etc.:  VII,  The  Stimulation  of  Pieces 
by  Section  in  Planaria  dorotocephala,^^  Jour,  oj  Exp.  Zool.,  X\T. 

1914ft.  "Studies  on  the  Dynamics,  etc.:  VIII,  Dynamic  Factors  in  Head- 
Determination  in  Planaria,"  Jour,  of  Exp.  Zool.,  XVII. 


CHAPTER  VI 

THE  RELATION  BETWEEN  AGAMIC   REPRODUCTION   AND   RE- 
JUVENESCENCE IN  THE  LOWER  ANIMALS 

THE  PROCESS  OF  AGAMIC  REPRODUCTION  IN  Platiaria  dorotocephala 

AND  RELATED  FORMS 

Planaria  dorotocephala,  like  many  other  species  of  flatworms, 
undergoes  from  time  to  time  a  process  of  agamic  or  asexual  repro- 
duction, which  consists  in  the  separation  by  fission  of  the  posterior 
third  or  fourth  of  the  body  from  the  rest  and  its  development  into 
a  new  animal.  The  posterior  region  which  separates  is  not  morpho- 
logically distinguishable  in  any  way  from  adjoining  regions  of  the 
body,  yet  the  separation  occurs  at  a  more  or  less  definite  level  of 
the  body. 

In  the  course  of  an  extended  study  of  experimental  reproduc- 
tion in  Planaria  I  have  found  that  the  posterior  body  region  in  all 
except  very  young  animals,  while  not  morphologically  distinguish- 
able as  a  new  individual,  is  nevertheless  clearly  marked  off  physio- 
logically from  the  region  anterior  to  it.  Along  the  main  axis  of 
the  planarian  body  a  gradient  in  the  rate  of  metabolism  exists 
(Child,  'i2,  '13a),  the  rate  being  highest  in  the  head-region  and 
decreasing  posteriorly  to  the  region  where  separation  occurs  in 
fission:  here  a  sudden  rise  in  rate  occurs,  and  posterior  to  this 
point  another  gradient  similar  to  that  in  the  anterior  region.  That 
is,  the  posterior  region  of  the  body,  which  is  separated  from  the 
rest  by  the  act  of  fission,  possesses  an  axial  gradient  in  rate  of  metab- 
ohsm  similar  to  that  of  the  anterior  region.  In  long  worms,  two, 
three,  or  even  more  of  these  metabolic  gradients  may  appear,  one 
posterior  to  the  other.  These  metabolic  gradients  in  the  body  of 
Planaria  appear,  not  only  in  the  susceptibility  of  different  regions, 
but  also  in  the  differences  in  the  capacity  for  reconstitution  of 
pieces  from  different  levels  (Child,  '116,  'iic). 

The  existence  of  these  metabolic  gradients  in  the  posterior 
region  of  Planaria  indicates,  as  chap,  ix  will  show  more  clearly, 

122 


AGAMIC  REPRODUCTION  AND  REJUVENESCENCE   123 


that  this  region  has  undergone 
the  first  step  in  the  process  of 
individuation.  Each  one  of  the 
gradients  is  the  dynamic  expres- 
sion of  this  individuation.  In 
fact,  the  body  of  Flanaria,  after 
a  certain  stage  of  development, 
is  physiologically  a  chain  of  two 
or  more  zooids,  i.e.,  of  individ- 
uals organically  connected.  In 
young  animals  four  or  five  miUi- 
meters  long  only  two  zooids  are 
distinguishable,  the  longer, 
anterior  zooid  making  up  the 
greater  part  of  the  body  and 
bearing  the  head,  and  the 
shorter,  posterior  zooid  indi- 
cated only  dynamically  by  a 
second  metabolic  gradient  in  the 
posterior  region.  The  boundary 
between  the  two  zooids  in  these 
small  animals  is  indicated  by 
the  dotted  line  across  the  body 
in  Fig.  28.  As  the  animal  be- 
comes longer,  other  zooids  arise 
in  the  posterior  region  by  fur- 
ther physiological  division  of 
the  original  posterior  zooid,  and 
when  it  has  reached  a  length  of 

Figs.  28-30. — Development  of  zooids 
in  Planaria  dorotoccphala:  Fig.  28,  a 
young  animal  with  two  zooids,  /  and  2; 
Fig.  29,  a  half-grown  animal  in  which 
the  original  posterior  zooid  has  divided 
into  zooids  2.1.  and  2.2.,  and  2.2.  has 
undergone  further  division;  Fig.  30,  a 
full-grown  animal  in  which  still  further 
zooids  have  appeared. 


/./. 


1.2. 


2.1.1. 


2.1. 


2.2. 


2.1.2. 


2.2.^ 


30 


124 


SENESCENCE  AND  REJUVENESCENCE 


ten  or  twelve  millimeters  the  posterior  region  is  more  or  less  clearly 
marked  off  by  metabolic  gradients  into  two  or  more  zooids 
(Fig.  29),  and  the  extreme  posterior  end  appears  to  be  a  growing 
tip  in  which  new  zooids  are  arising.     In  nature,  separation  at  the 

boundary  between  the  first  and  second  zooids 
very  commonly  occurs  at  about  this  stage, 
but  if  the  animals  are  prevented  from  divid- 
ing, which  may  be  accomplished  in  various 
ways,  they  may  grow  to  a  length  of  twenty- 
five  to  thirty  millimeters  and  the  posterior 
region  may  consist  of  four  to  five  zooids  and 
a  growing  tip  (Fig.  30). 

The  dynamic  demarkation  of  these  pos- 
terior zooids  results,  as  has  been  shown  else- 
where,' from  a  physiological  isolation  of  the 
regions  concerned  in  forming  the  dominant 
head-region  of  the  animal.  The  consequence 
of  this  physiological  isolation  is  the  beginning 
of  a  new  individuation  in  the  isolated  region, 
in  essentially  the  same  manner  as  in  the 
physically  isolated  piece  which  begins  to 
undergo  reconstitution,  and  for  the  same 
reason.  But  the  physiological  isolation  of 
the  posterior  region  of  the  planarian  body  is 
less  complete  than  in  the  piece  isolated  by 
section;  consequently  the  development  of 
new  individuation  beyond  a  very  early  stage, 
which  is  only  dynamically  distinguishable,  is 
inhibited.  In  Planaria  maculata  and  various 
other  species  of  Planaria  new  zooids  arise  in 
the  same  way  and  exist  dynamically  as  axial 
gradients,  but  their  morphological  develop- 
ment is  similarly  inhibited  until  after  their  physical  separation 
from  more  anterior  regions. 

The  act  of  fission  in  these  animals  results  from  an  independent 
motor  reaction  of  posterior  and  anterior  zooids.     If  the  animal  is 

'  Child,  '10,  'iia,  'lie;   see  also  chap.  ix. 


Fig.  31. — Planaria 
dorotocephala  in  process 
of  division. 


AGAMIC  REPRODUCTION  AXD  REJU\'EXESCENCE        12 


D 


slightly  stimulated  when  creeping  about,  or  in  some  cases  without 
any  stimulation  from  external  sources  being  apparent,  the  posterior 
region  suddenly  attaches  itself  tightly  to  the  underlying  surface 
by  its  margins,  using  the  ventral  surface  as  a  sucking  disk,  while 
the  anterior  zooid  continues  to  creep,  and  when  it  feels  the  resist- 
ance to  forward  movement  it  exerts  itself  violently  to  pull  away. 
The  consequence  of  this  lack  of  co-ordination  between  the  two 
regions  is  that  the  body  just  anterior  to  the  attached  region  be- 
comes more  and  more  stretched  and  tinally  ruptures,  and  the 
posterior  region  is  left  behind.  Fig.  31  shows  an  animal  in  the  act 
of  fission.  The  anterior  zooid  bearing  the  head  is  endeavoring  to 
move  forward,  and  the  posterior  zooid  has  attached  itself  firml>- 
to  the  surface  on  which  the  animal  was  creeping.  In  many  cases 
the  posterior  region  of  the  first  zooid  becomes  stretched  into  a  long, 
slender  band,  and  even  then,  particularly  in  large  old  animals 
where  the  tissues  seem  to  be  tougher  and  rupture  less  readily,  the 
anterior  zooid  often  apparently  becomes  exhausted  and  ceases  to 
exert  itself,  or  else  the  posterior  zooid  is  torn  from  its  attachment 
to  the  substratum  or  releases  itself  before  the  connecting  parts  are 
ruptured.  Such  failures  of  fission  are  very  common  in  the  larger, 
older  animals.  Fission  can  also  be  prevented  by  keeping  the  ani- 
mals on  surfaces  to  which  they  cannot  attach  themselves  firml\-, 
e.g.,  in  vaseline-lined  dishes. 

After  separation  the  smaller  posterior  piece  undergoes  reconsti- 
tution  into  a  new  animal  of  small  size  in  exactly  the  same  manner 
as  do  pieces  cut  from  the  body,  and  the  anterior  zooid  develops  a 
new  posterior  end  in  which  one  or  more  new  zooids  may  arise.  In 
Planaria  dorotocephala  this  is  the  only  form  of  reproduction  which 
has  been  observed  in  nature  during  a  period  of  observation  covering 
some  ten  years,  but  in  the  laboratory,  animals  which  have  been 
prevented  from  undergoing  fission  have  become  sexually  mature 
in  a  few  cases. 


THE  OCCURRENCE  OF  REJUVENESCENCE  IN  AG.\MIC  REPRODUCTION 

IN  Planaria  dorotocephala  and  P.  maculata 

Since  a  greater  or  less  degree  of  rejuvenescence  occurs  in  the 
reconstitution  of  pieces  of  Planaria  (see  chap,  v)  and  since  the 


126 


SENESCENCE  AND  REJUVENESCENCE 


u 


a 


\i 


33 


Figs.  32-34. — Reconstitution  after  fission  in 
Planaria  dorotocephala:  Fig.  32,  animal  before 
fission;  ff,  fission-plane,  a,  anterior,  b,  posterior 
zooid;  Fig.  S3,  reconstitution  of  posterior  zooid; 
Fig.  34,  reconstitution  of  anteriorzoord. 


natural  process  of  agamic 
reproduction  resembles  so 
closely  the  process  of 
reconstitution  the  occur- 
rence of  some  degree  of 
rejuvenescence  is  to  be 
expected  in  agamic  repro- 
duction. 

It  has  already  been 
shown  in  Fig.  3  (p.  80) 
and  in  Fig.  13  (p.  100)  that 
individuals  of  P.  doroto- 
cephala of  small  size  and 
young  in  appearance,  but 
which  supposedly  arose 
agamically,  are  physiologi- 
cally much  younger  as  re- 
gards their  susceptibility 
than  the  large,  apparently 
old  animals.  But  in  order 
to  obtain  conclusive  evi- 
dence upon  this  point  it  is 
necessary  to  compare  ani- 
mals which  are  known  to 
have  arisen  by  fission 
under  controlled  con- 
ditions with  animals  hke 
those  in  which  the  fission 
occurred. 

This  comparison  has 
been  made  repeatedly  and 
the  result  confirms  expec- 
tation. The  small  animal 
which  develops  from  the 
separated  posterior  region 
of  the  parent  animal  is 
physiologically     much 


AGAMIC  REPRODUCTION  AND  REJU\ENESCEXCE        127 

younger  than  the  latter.  Since  the  results  of  these  experiments 
are  in  all  respects  essentially  identical  with  those  obtained  with 
pieces  artificially  isolated  by  section,  it  is  unnecessary  to  present 
them  in  detailed  form. 

In  the  process  of  fission  the  separated  posterior  zooid  undergoes 
much  more  extensive  reorganization  than  the  anterior  zooid.  In 
an  animal  of  medium  size  fission  usually  occurs  at  about  the  level 
indicated  by  the  line/  in  Fig.  32.  The  posterior  piece  b  (Fig.  32) 
is  much  smaller  than  the  anterior  a,  and  it  develops  a  new  head  and 
a  new  pharynx,  and  extensive  changes  in  the  alimentary  tract 
occur  in  the  formation  of  the  prepharyngeal  region.  Moreover, 
it  cannot  take  food  until  the  new  mouth  and  pharynx  have  reached 
a  certain  stage  of  development,  consequently  the  energy  for  develop- 
ment is  derived  from  its  own  tissues  and  it  undergoes  more  or 
less  reduction  during  the  process.  In  Fig.  t^t^  the  animal  developed 
from  the  posterior  fission-piece  is  drawn  to  the  same  scale  as  Fig.  32. 
This  animal  is  physiologically  much  younger  than  the  parent  from 
which  it  came.  Its  susceptibility  is  much  higher  and  it  is  capable 
of  more  rapid  growth  than  the  original  animal. 

In  the  anterior  fission-piece  (a,  Fig.  32),  on  the  other  hand,  the 
original  head  and  the  mouth  and  pharynx  persist,  "the  only  out- 
growth of  new  tissue  formed  is  at  the  posterior  end,  and  the  only 
other  change  in  form  is  the  growth  of  the  postpharyngeal  at  the 
expense  of  the  prepharyngeal  region,  in  consequence  of  which  the 
pharynx  seems  to  migrate  forward  (Fig.  34).  When  food  is  present, 
this  piece  may  feed  and  increase  in  size  during  the  whole  process 
of  reconstitution,  but  even  when  it  is  not  fed,  the  degree  of  reduction 
during  reconstitution  is  slight,  because  the  developing  regions  have 
a  relatively  large  mass  to  draw  upon  as  a  source  of  energy.  The 
relation  which  was  shown  in  the  preceding  chapter  to  exist  between 
the  size  of  the  piece,  the  amount  of  reconstitutional  change,  and  the 
amount  of  increase  in  susceptibility  would  lead  us  to  e.xpcct  that 
the  increase  in  susceptibility  resulting  from  the  reconstitutional 
changes  in  the  anterior  fission-piece  would  be  much  less  than  in  the 
posterior  piece,  and  this  is  in  fact  the  case. 

The  increase  in  susceptibility  in  the  posterior  piece  is  the  same 
as  that  in  artificially  isolated  pieces  of  the  same  size.     In  Plauaria 


128 


SENESCENCE  AND  REJUVENESCENCE 


maculata  the  animals  developed  from  these  pieces  are  about  as 
young  physiologically  as  sexually  produced  animals  of  the  same 
size.  In  P.  dorotocephala,  where  sexually  produced  animals  are 
not  available  for  comparison,  the  degree  of  increase  in  suscepti- 
bility over  that  of  the  parent  animals  is  about  the  same  as  in  P. 
maculata.  Since  these  results  are  so  completely  in  agreement, 
both  with  expectation  and  with  the  results  obtained  from  arti- 
ficially isolated  pieces,  experimental  records  are  unnecessary. 

Stages  i  ^  (^ 


II 


III 


IV 


Hours  2345678 

Fig.  35. — Susceptibility  of  Planaria  dorotocephala  to   KCN   o.ooi    mol. 
anterior  fission-pieces  after  reconstitution;   cd,  entire  animals  before  fission. 


ah. 


With  respect  to  the  anterior  fission-piece,  however,  it  is  a  matter 
of  some  interest  to  demonstrate  that  the  reconstitutional  changes 
occurring  in  the  posterior  region  of  so  large  a  piece  as  this  do  alter 
the  physiological  condition  of  the  whole  piece,  including  even  the 
head-region.  For  this  reason  the  record  of  one  susceptibility  test 
of  these  anterior  pieces  is  given  in  Fig.  35.  For  this  experiment 
worms  ten  to  twelve  millimeters  in  length  were  induced  to  undergo 
fission  and  the  anterior  fission-pieces  were  kept  without  food  for 
twelve  days.     Another  lot  of  worms  of  the  same  size  and  in  the 


AGAMIC  REPRODUCTION  AND  REJUVENESCENCE        129 

same  physiological  condition,  bul  undivided,  was  kept  without 
food  during  the  same  period  as  a  control.  In  Fig.  35,  curve  ab 
shows  the  susceptibility  of  the  anterior  fission-pieces,  curve  cd 
that  of  ten  of  the  undivided  animals,  also  without  food.  At  this 
time  the  animals  had  attained  the  stage  of  development  shown  in 
Fig.  34- 

The  susceptibihty  of  the  fission-pieces  is  distinctly  greater 
than  that  of  the  undivided  animals,  and  as  a  matter  of  fact  the 
differences  are  greater  than  the  curves  show.  At  the  points  in  the 
curve  where  the  two  lots  appear  to  be  in  the  same  or  nearly  the 
same  stage  of  disintegration,  examination  of  the  pieces  showed 
that  even  though  the  two  lots  might  fall  within  the  same  one  of 
the  five  arbitrarily  distinguished  stages,  the  fission-pieces  were 
always  more  advanced  in  that  stage.  The  fission-pieces  are  evi- 
dently younger  physiologically  than  whole  worms,  and  this  is  true, 
not  only  for  the  posterior  region  where  the  reconstitutional  changes 
are  localized,  but  for  the  whole  body,  including  the  head.  Un- 
doubtedly the  anterior  regions  have  served  to  some  slight  extent 
as  a  source  of  energy  for  the  developmental  changes  in  the  posterior 
region. 

Similar  results  have  been  obtained  repeatedly  in  other  similar 
experiments.  If  the  anterior  fission-pieces  are  fed  during  recon- 
stitution  and  their  susceptibility  compared  with  that  of  whole 
animals  fed  at  the  same  time,  the  increase  in  susceptibility  is  found 
to  be  less  marked  or  inappreciable.  In  such  cases  the  food  taken, 
rather  than  the  tissues,  provides  the  energy  for  the  development 
of  the  new  posterior  end.  Similarly  the  larger  the  animal  when 
division  occurs,  the  less  the  increase  in  susceptibility.  In  the  very 
large,  heavily  fed  animals,  in  which  the  anterior  tission-picce  may 
be  fifteen  millimeters  or  more  in  length,  there  is  usually  no  appre- 
ciable increase  in  susceptibility  in  this  piece  after  fission.  Here 
the  amount  of  reconstitutional  change  is  so  slight  in  relation  to 
the  size,  and  the  amount  of  nutritive  reserve  is  so  great,  that  the 
body  as  a  whole  is  not  appreciably  affected  by  the  development 
of  the  posterior  end. 

The  relation  between  agamic  reproduction  and  susceptibility 
is  the  same  in  Planaria  dorotoccphala  and  in  /'.  maciilata.     In  both 


130  SENESCENCE  AND  REJUVENESCENCE 

species  the  posterior  fission-piece  undergoes  a  considerable  increase ; 
the  anterior,  except  when  very  large  or  heavily  fed,  exhibits  a 
shght  increase  in  susceptibility.  In  other  words,  agamic  repro- 
duction brings  about  a  greater  or  less  degree  of  rejuvenescence. 

AGAMIC  REPRODUCTION  AND  REJUVENESCENCE  IN  Plauaria  velata 

Planaria  velata  (Fig.  8),  a  flatworm  found  very  commonly  in 
temporary  pools  and  ditches  as  well  as  sometimes  in  permanent 
bodies  of  water,  is  another  species  in  which  only  agamic  or  asexual 
reproduction  has  been  observed  during  some  thirteen  years.  The 
asexual  cycle  of  this  species  and  its  relation  to  senescence  and  re- 
juvenescence have  been  considered  at  length  elsewhere  (Child, 
'13&,  '14),  and  only  the  more  important  points  need  be  reviewed  here. 

Agamic  reproduction  in  this  species  is  a  process  of  fragmenta- 
tion which  occurs  only  at  the  end  of  the  growth  period.  The 
animals  appear  early  in  spring,  chiefly  in  temporary  pools  and 
ditches  in  which  dead  leaves  have  accumulated.  When  they  first 
appear  they  are  only  two  or  three  millimeters  in  length,  very  active, 
and  to  all  appearances  young  in  every  respect.  They  grow  rapidly 
and  become  deeply  pigmented,  but  the  rate  of  growth  gradually 
decreases,  and  at  the  end  of  three  or  four  weeks,  when  they  have 
attained  a  length  of  about  fifteen  millimeters,  they  cease  to  feed, 
become  lighter  in  color,  their  motor  activity  undergoes  a  distinct 
and  progressive  decrease,  and  the  pharynx  undergoes  complete 
disintegration.  Within  a  few  days  after  these  changes  fragmenta- 
tion begins  at  the  posterior  end  of  the  body.  The  process  of 
fragmentation  resembles  in  certain  respects  the  process  of  fission 
in  P.  dorotocephala,  described  in  the  first  section  of  this  chapter. 
As  in  that  species,  the  act  of  separation  is  accomplished  by  attach- 
ment of  the  posterior  end  to  the  substratum  while  the  animal  is 
creeping,  with  the  result  that  a  small  piece  tears  off  and  is  left  behind. 
But  in  P.  velata  the  process  may  be  repeated  frequently  in  the  course 
of  a  few  hours  and  the  fragments  vary  widely  in  size.  In  P.  velata, 
as  in  P.  dorotocephala,  fragmentation  is  undoubtedly  the  result  of 
physiological  isolation  and  independent  motor  reaction  of  the 
posterior  end  of  the  body,  but,  instead  of  occurring  periodically 
during  the  life  of  the  animal,  it  does  not  occur  until  senescence  is 


AGAMIC  REPRODUCTION  AND  REJUVENESCENCE        131 

far  advanced  and  the  rate  of  metabolism  is  very  low.  Posterior 
zooids  are  not  distinctly  marked  off  dynamically,  as  in  P.  doroto- 
cephala,  but  the  portions  which  separate  are  merely  small  bits  cjf 
the  body  at  the  posterior  end  which,  as  the  animal  becomes  pro- 
gressively weaker,  finally  cease  to  be  controlled  and  co-ordinated 
with  other  parts  by  the  dominant  head-region,  and  so,  sooner  or 
later,  react  independently  and  are  torn  off.  In  some  cases  the 
animal  may  leave  a  trail  of  such  fragments  behind  it  as  it  creeps 
slowly  along.  The  stimulation  resulting  from  the  rupture  of  the 
tissues  leads  to  the  secretion  of  slime  on  the  surface  of  the  separated 
pieces,  and  this  slime  hardens  and  forms  a  cyst  within  which  the 
pieces  gradually  undergo  reconstitution  to  whole  animals  of  small 
size  which  sooner  or  later  emerge. 

Fragmentation  may  continue  until  only  the  head  and  a  short 
piece  of  the  body  two  or  three  millimeters  in  length  remain,  or  it 
may  be  confined  to  the  posterior  third  or  half  of  the  body.  After 
fragmentation  is  completed,  the  anterior  piece,  whether  large  or 
small,  may  encyst,  or  it  may  remain  more  or  less  active  and  grad- 
ually undergo  reduction  in  size  in  consequence  of  starvation. 
Finally,  after  considerable  reduction  has  occurred,  it  develops  a 
new  pharynx  and  mouth  and  a  new  posterior  end,  and  begins  to 
feed  and  grow  again.  Cases  of  this  sort  will  be  considered  in 
chap,  vii. 

The  encysted  fragments  do  not  withstand  complete  desiccation, 
but  the  bottoms  of  the  ditches  and  pools  in  which  they  live  retain 
sufficient  moisture  to  keep  them  aHve.  In  the  autumn  the  ditches 
do  not  usually  fill  again  before  cold  weather,  although  they  may  do 
so,  in  which  case  the  worms  may  emerge  from  the  cysts  at  that 
time,  but  their  growth  is  soon  stopped  by  low  temperature.  Com- 
monly, however,  they  appear  only  in  spring,  as  soon  as  the  ditches 
thaw  out.  This  cycle  is  repeated  year  after  year,  and  thus  far 
neither  sexually  mature  animals  nor  animals  with  any  part  of  the 
sexual  ducts  or  copulatory  organs  have  ever  been  found,  though 
ovaries  and  testes  in  early  stages  of  development  may  sometimes 
be  present. 

In  the  laboratory  the  animals  may  pass  through  the  whole  life 
cycle  in  two  or  three  months,  for  the  encysted  fragments  wlun 


132 


SENESCENCE  AND  REJUVENESCENCE 


kept  in  water  often  emerge  as  young  worms  within  two  or  three 
weeks  after  encystment.  There  is  therefore  no  difhculty  in  ob- 
taining small  animals  which  are  known  to  have  developed  from 
encysted  pieces  for  comparison  with  the  larger  animals  at  various 
stages  of  the  life  cycle. 

Fig.  36  shows  the  susceptibility  of  ten  animals  about  two  milli- 
meters in  length  newly  emerged  from  cysts  (curve  ah)  compared 
with  that  of  ten  full-grown  animals  raised  from  cysts  in  the  labora- 


Stages 


Hours  1234567 

Fig.  36. — Susceptibility  of  Planaria  velata  to  KCN  o.ooi    mol.:   ah,    animals 
newly  emerged  from  cysts;  cd,  full-grown  animals. 

tory  (curve  cd).  The  susceptibility  of  the  small,  newly  emerged 
animals  is  very  much  greater  than  that  of  the  full-grown  animals. 
In  other  words,  the  newly  emerged  worms  are  young  as  regards 
rate  of  metabolism,  as  they  appear  to  be  in  every  other  respect,  and 
the  full-grown  animals  which  are  about  to  undergo  fragmentation 
are  old.  In  this  species,  as  in  P.  dorotocephala,  agamic  reproduction 
is  simply  a  separation  and  reconstitution  of  pieces,  and  rejuvenes- 
cence is  associated  with  the  reconstitutional  changes  in  the  piece. 


AGAMIC  REPRODUCTION  AND  REJUVENESCENCE        133 

Since  the  pieces  are  usually  vety  small,  the  reorganization  is  ex- 
tensive and  the  degree  of  rejuvenescence  is  ver}-  much  greater  than 
in  the  larger  pieces  separated  in  agamic  reproduction  in  P.  doroto- 
cephala  and  P.  maculata.  In  cases  where  large  instead  of  small 
fragments  are  formed  the  animals  which  develop  from  them  are  of 
course  longer  than  those  from  the  small  fragments,  the  reconsti- 
tutional  changes  are  less  extensive,  and  the  degree  of  rejuvenescence 
is  less  than  in  the  small  fragments. 

Apparently  the  degree  of  rejuvenescence  is  essentially  the  same 
in  successive  generations,  for  this  method  of  reproduction  is  ade- 
quate for  the  maintenance  of  the  species  without  visible  decrease 
in  vigor  or  advance  in  senescence,  at  least  for  a  considerable  number 
of  generations.  In  the  laboratory  a  stock  of  these  worms  has  been 
bred  asexually  over  three  years  and  has  passed  through  fifteen 
generations  without  any  apparent  progressive  change  in  the 
physiological  condition  of  the  animals  in  successive  generations. 
In  each  generation  the  rate  of  metabolism  decreases  and  the  process 
of  senescence  ends  in  fragmentation  and  encystment,  and  young 
animals  emerge  from  the  cysts  and  repeat  the  life  cycle. 

This  case  is  of  particular  interest  because  the  process  of  senes- 
cence, as  it  occurs  under  the  usual  conditions  of  existence,  does  not 
end  in  death  but  leads  directly  to  reproduction  and  rejuvenescence. 
The  occurrence  of  fragmentation  in  these  animals  is  ver>'  clearly 
associated  with  the  decrease  in  rate  of  metabolism  which  is  the 
characteristic  dynamic  feature  of  senescence  (Child,  '136).  As 
the  animal  grows  old  its  decreasing  rate  of  metaboKsm  makes  im- 
possible the  maintenance  of  physiological  individuality.  Physio- 
logical isolation  of  parts  (see  chap,  ix)  occurs  and  is  followed  by 
physical  isolation,  and  the  isolated  parts  of  the  old  individual 
undergo  reconstitution  into  new,  young  individuals.  Senescence 
itself  is  the  physiological  factor  inducing  reproduction  and  re- 
juvenescence. 

AGAMIC  REPRODUCTION  AND  REJUVENESCENCE  IN  StCHOStomum 

AND  CERTAIN  ANNELIDS 

In  certain  flatworms,  among  which  is  the  genus  Stcnosiomum, 
the    morphological    development   of    the   new   zooids   reaches   an 


134 


SENESCENCE  AND  REJUVENESCENCE 


advanced  stage  before  they  separate  from  the  parent  body.     In 
such  forms  the  body  consists  visibly  of  a  chain  of  zooids  in  various 


A 


/./. 


1.2. 


38 


I.J.I. 


J. 1.2. 


> i 


1.2. 


2.1. 


?  <\ 


2.2. 


39 


I.I.I. 


1. 1. 2. 


1.2.1. 


1.2.2. 


2. 1. 1. 


2.1.2. 


2.2. 


Figs.  37-40. — Progress  of  agamic  reproduction  in  Stciw- 
stomum:  the  sequence  in  the  formation  of  new  zooids  is  indi- 
cated by  the  numerals. 


40 


stages  of  development.  The  development  of  such  a  chain  of 
zooids  in  Stenostomiim  is  shown  in  Figs.  37-40.  In  Fig.  37  only 
the  zooids  i  and  2  are  present;  in  Fig.  38  zooid  i  has  divided  into 


AGAMIC  REPRODUCTION  AND  RPJUVENESCENCE        135 

I.I.  and  1 .  2 . ,  but  zooid  2  has  not  yet  divided.  In  Fig.  39  zooid 
I.I.  has  divided  again  into  i .  i .  i.  and  1.1.2.,  zooid  1.2.  has  not 
yet  divided,  and  zooid  2.  has  divided  into  2.1.  and  2.2.  In  Fig.  39 
still  further  divisions  have  occurred,  and  the  relations  of  the  dilTer- 
ent  zooids  are  indicated  by  the  numbers  designating  each.  Here 
morphological  development  of  each  zooid  is  almost  completed 
before  separation  occurs.  The  first  separation  takes  place  at  the 
most  advanced  fission-plane  and  as  other  zooids  reach  a  correspond- 
ing stage  other  separations  occur,  but  meanwhile  new  zooids  have 
begun  to  develop.  Thus  the  breaking  up  of  the  old  chains  and  the 
formation  of  new  go  hand  in  hand. 

Such  processes  of  agamic  reproduction  do  not  differ  essentially 
in  any  way  from  the  process  of  reconstitution  of  pieces  isolated  by 
section  in  the  same  species.  In  both  cases  a  certain  region  of  the 
body  gradually  transforms  itself  into  a  w'hole  animal.  In  both 
cases  certain  parts  atrophy  and  disappear,  cell  division  and  localized 
growth  occur,  and  new  parts  develop.  In  Slenoslomunu  however, 
the  new  zooid  receives  food  during  its  development,  for  the  ali- 
mentary tract  common  to  the  whole  chain  passes  through  it;  con- 
sequently it  is  not  dependent  upon  its  own  tissues  for  the  energy 
necessary  for  its  development  as  is  a  physically  isolated  piece,  and 
therefore  it  does  not  undergo  the  reduction  in  size  characteristic 
of  such  pieces.  In  fact  it  usually  increases  in  size  during  develop- 
ment. 

In  Stenostomuni  as  in  Planar ia  the  susceptibilii}'  method 
demonstrates  the  existence  of  a  longitudinal  a.xial  gradient  in  rate 
of  metaboHsm.  Before  agamic  reproduction  begins  this  gradient 
extends  the  length  of  the  individual,  but  as  new  zooids  arise  the 
anterior  region  of  each  shows  a  higher  rate  of  metabolism  than  the 
region  immediately  anterior  to  it,  and  each  zooid  develops  its  own 
axial  gradient  like  that  of  the  original  animal.  In  the  earlier  stages 
of  zooid  development  the  susceptibility  of  the  new  zooid  is  less, 
i.e.,  its  rate  of  metabolism  is  lower,  than  that  of  the  fully  developed 
zooid  which  heads  the  chain,  but  as  development  proceeds  the  sus- 
ceptibility increases,  until  at  the  time  of  separation,  or  soon  after, 
it  is  higher  than  that  of  the  anterior  zooid.  Separation  of  the 
zooids  at  an  earlier  stage  of  development  than  that  at  which  it 


136  SENESCENCE  AND  REJUVENESCENCE 

naturally  occurs  may  be  induced  by  strong  stimulation,  and  in  such 
cases  development  and  the  increase  in  susceptibility  are  usually 
somewhat  accelerated. 

From  these  facts  we  must  conclude  that  in  Stcnostomuni  as  in 
Planaria  the  reconstitution  of  a  given  region  of  the  body  into  a 
new  individual  is  accompanied  by  some  degree  of  physiological 
rejuvenescence.  Without  doubt  the  age  differences  in  suscepti- 
bility between  the  developing  young  zooids  and  the  fully  developed, 
relatively,  old  anterior  zooid  of  the  chain  are  obscured  to  some  extent 
by  the  much  greater  motor  activity  of  the  latter,  but  the  fact  that 
sooner  or  later  the  young  zooids  become  more  susceptible  than  this 
older  zooid  indicates  that  rejuvenescence  does  occur. 

In  various  species  of  aquatic  oligochete  annelids  agamic  repro- 
duction occurs  in  much  the  same  manner  as  in  Stenostomum.  In 
the  course  of  investigations  as  yet  unpublished  Miss  Hyman  has 
found  that  these  animals,  like  the  flatworms,  undergo  a  greater  or 
less  degree  of  physiological  rejuvenescence  in  connection  with 
agamic  reproduction. 

THE  RELATION  BETWEEN  AGAMIC  REPRODUCTION  AND  REJUVENES- 
CENCE IN  PROTOZOA 

The  question  whether  the  protozoa  undergo  senescence  or  not  is 
of  considerable  interest  at  present.  The  generally  accepted  view 
based  on  the  researches  of  Maupas  ('88,  '89)  that  conjugation  in 
the  ciliate  infusoria  terminates  an  invariable  process  of  race  senes- 
cence and  brings  about  rejuvenescence  requires  some  modification 
in  the  light  of  recent  researches.  Woodruff  has  bred  a  race  of 
Paramecium  through  nearly  five  thousand  generations  without 
conjugation  and  without  loss  of  vigor.'  This  number  of  gen- 
erations is  so  large  that  we  are  justified  in  maintaining  that 
for  the  race  of  Paramecium  used,  and  under  the  conditions  of 
experiment,  conjugation  is  not  an  essential  feature  of  the  life 
cycle.     On   the   other  hand,   various   investigators^   have   shown 

'Woodruff,  '08,  '09,  'no,  '13a,  '13^,  '14;  Woodruff  and  Erdmann,  '14.  In 
these  and  other  papers  the  author  records  the  progress  of  the  agamic  breeding. 

=  Among  these  may  be  mentioned  Calkins,  'o2ff,  '026,  '04;  Enriques,  '03,  '07, 
'08;  Woodruff  (see  note  i);  Jennings,  '10,  '13;  Baitsell,  '12,  '14;  Zweibaum,  '12; 
Calkins  and  Gregory,  '13. 


AG.UIIC  REPRODUCTION  AND  REJU\'ENESCENCE        137 

during  the  last  few  years  that  the  occurrence  of  conjugation 
is  dependent,  at  least  in  a  large  measure,  upon  external  factors. 
Woodruff  has  experimentally  induced  conjugation  in  members  of 
his  culture  which  has  been  agamically  bred  through  thousands  of 
generations.  Jennings  concludes  from  extended  experimentation 
that  conjugation  does  not  bring  about  rejuvenescence,  but  merely 
increases  variabihty,  while  Calkins  and  Gregory  beheve  that  reju- 
venescence does  occur,  at  least  in  some  cases. 

If  conjugation  is  not  a  necessary  feature  of  the  life  cycle,  or  if 
it  fails  to  accomplish  rejuvenescence,  two  alternative  conclusions 
present  themselves:  either  these  animals  do  not  necessarily  undergo 
senescence  or  else  rejuvenescence  is  accomplished  in  some  other 
way  than  by  conjugation.  The  relation  found  to  exist  between 
agamic  reproduction  and  rejuvenescence  in  the  flatworms  suggests 
at  once  the  possibihty  that  a  similar  relation  may  exist  in  the 
protozoa. 

Since  the  protozoa  are  unicellular  animals,  agamic  reproduction 
is  essentially  a  process  of  cell  division,  but  since  it  is  also  true  that 
at  least  many  protozoa  possess  a  more  or  less  complex  morphological 
structure,  agamic  reproduction,  as  in  multicellular  forms,  resembles 
the  process  of  reconstitution  in  that  it  involves  various  morpho- 
logical changes,  consisting  in  the  dedift'erentiation  and  disappear- 
ance of  certain  structures  and  the  formation  and  development  of 
others.  In  Paramecium,  for  example,  agamic  reproduction  does 
not  consist  merely  in  nuclear  and  cytoplasmic  division,  but  exten- 
sive reorganization  also  occurs.  In  Figs.  41-43  the  most  important 
changes  are  diagrammatically  represented.  Fig.  41  shows  the 
animal  before  division,  the  oral  groove,  og,  the  pharynx,  p,  and  the 
two  vacuoles,  v,  being  indicated  in  the  figure,  as  well  as  the  meganu- 
cleus,  mg,  and  the  micronucleus,  mc.  The  first  indications  of 
division  are  cytoplasmic,  not  nuclear,  and  consist  in  the  formation 
of  a  new  contractile  vacuole  in  what  is  to  become  the  anterior  region 
of  each  individual,  the  two  vacuoles  of  the  parent  individual  becom- 
ing the  posterior  vacuoles  in  the  daughter  animals  and  new  vacuoles, 
v'v' ,  appearing  in  the  anterior  region  of  each.  The  mouth  and 
pharynx  and  the  posterior  portion  of  the  oral  groove  undergo  more 
or  less  change  and  become  parts  of  the  posterior  daughter  animal, 


138 


SENESCENCE  AND  REJUVENESCENCE 


while  in  the  anterior  daughter  animal  a  new  mouth  and  pharynx 
and  probably  a  new  oral  groove  arise  (Fig.  42),  while  both  mega- 
nucleus  and  micronucleus'  undergo  division  (Fig.  42),  the  process 
in  the  former  being  apparently  a  direct  or  amitotic  division,  while 
in  the  latter  it  resembles  the  process  of  mitosis  in  certain  respects. 
Before  these  divisions  are  completed  a  transverse  constriction 
appears  at  about  the  middle  of  the  parent  body  (Fig.  42),  and  this 


mc 


10 


0 


o 


Figs.  41-43. — Three  stages  in  the  division  of  Faramecium:  mc,  micronucleus; 
mg,  meganucleus;  og,  oral  groove;  p,  pharynx;  v,  vacuoles  of  original  individual; 
v' ,  new  vacuoles. 

deepens  (Fig.  43),  until  finally  separation  of  the  two  daughter 
individuals  occurs  at  this  level.  Before  division  occurs  the  cyto- 
plasmic reorganization  has  reached  an  advanced  stage  (Fig.  42), 
but  the  development  of  the  oral  groove  and  the  attainment  of  the 
characteristic  proportions  are  not  completed  until  after  separation. 
In  Stentor  coeruleus  the  process  of  agamic  reproduction  differs 
in  certain  respects  from  that  in  Paramecium.  In  Stentor  the  first 
visible  stages  in  division  are  cytoplasmic,  as  in  Paramecium,  and 

'  In  the  caudatiim  group  of  Paramecium  only  one  micronucleus  is  present,  while 
in  the  aiirelia  group  there  are  two.  See  Jennings  and  Hargitt  ('10),  Woodruff  ('11^), 
for  the  characteristics  of  these  groups  or  species  of  Paramecium. 


AGAMIC  RErRODUCTION  AND  REJUVENESCENCE 


139 


consist  in  the  appearance  of  a  new  vacuole  near  the  middle  of  the 
body  and  the  development  of  a  band  of  peristomial  cilia  (Fig.  44), 


mg. 


Figs.  44-47. — Four  stages  of  division  in  Slcntor:  the  margin  of  both  old  and  new 
peristomes  is  indicated  by  a  heavy  line;  the  separation  of  the  new  vacuole,  r',  from  the 
old,  V,  and  the  changes  in  shape  of  the  meganucleus,  mg,  are  also  indicated  After 
Johnson,  '93. 


I40  SENESCENCE  AND  REJUVENESCENCE 

which  at  first  extends  almost  longitudinally.  After  these  changes 
have  occurred  the  elongated  moniliform  meganucleus,  mg,  under- 
goes concentration  to  a  spherical  form,  as  in  Fig.  45,  and  the  new 
peristomial  band  of  cilia  gradually  assumes  a  curved  outline.  Then 
a  transverse  constriction  appears  in  the  meganucleus,  which  defines 
two  approximately  equal  halves,  and  this  is  followed  by  elongation  of 
the  meganucleus  {mg,  Fig.  46),  but  separation  of  the  two  halves  does 
not  occur  until  later.  As  regards  the  micronuclei,  of  which  there 
are  usually  a  large  number  in  Stentor  (Johnson,  '93),  it  is  not  known 
whether  all  or  only  a  part  of  them  divide  in  each  fission.  The  new 
peristomial  band  of  cilia  changes  its  position,  becoming  more  nearly 
transverse  and  semicircular  in  outline  (Fig.  46),  and  a  mouth 
begins  to  develop  at  its  posterior  end.  This  change  in  shape  is 
accomplished  by  a  lateral  outgrowth  on  one  side  of  the  body  near 
the  middle  which  represents  the  anterior  end  and  the  peristome  of 
the  posterior  daughter  individual.  Just  anterior  to  this  develop- 
ing peristome  the  level  at  which  separation  will  occur  is  now  indi- 
cated by  a  constriction,  as  in  Fig.  46.  Other  changes,  indicated  in 
Figs.  46  and  47,  consist  in  the  further  development  of  the  new  per- 
istome and  its  continued  approach  to  the  transverse  position,  the 
deepening  of  the  constriction  between  the  two  individuals,  and  the 
breaking  up  of  the  meganucleus  into  the  characteristic  segments, 
beginning  at  the  two  ends.  Still  later  the  meganucleus  separates  at 
the  level  of  the  cytoplasmic  constriction,  which  continues  to  become 
deeper,  until  the  anterior  member  of  the  pair  is  attached  to  the 
peristome  of  the  posterior  member  only  by  a  slender  peduncle. 
This  finally  separates  and  the  process  of  fission  is  completed.  As 
regards  the  essential  features  of  the  process  of  fission,  other  species 
of  ciliates  resemble  Paramecium  and  Stentor,  but  the  details  of  recon- 
stitution  differ  for  each  species. 

The  process  of  fission  in  these  forms  has  been  described  at  some 
length  because  it  is  evident  that  it  is  a  much  more  complex  process 
than  ordinary  cell  division  in  the  metazoa.  So  far  as  the  cyto- 
plasmic structures  are  concerned  it  is  manifestly  a  process  of  recon- 
stitution  resembling  that  which  occurs  in  agamic  reproduction  in 
nature  and  in  isolated  pieces  in  the  flatworms  and  many  other 
metazoa.     Moreover,   the  process  differs  in  the  two  forms.     In 


AGAMIC  REPRODUCTION  AND  REJUVENESCEXCK         141 

Paramecium,  the  original  mouth  becomes,  with  more  or  less  reorgani- 
zation, the  mouth  of  the  posterior  daughter  individual  and  a  new 
mouth  arises  in  the  anterior  individual,  while  in  Slcntor  the  original 
mouth  and  peristome  remain  as  a  part  of  the  anterior  individual 
and  the  new  peristome  is  that  of  the  posterior  individual.  And, 
finally,  extensive  developmental  changes  occur  in  the  cytoplasm 
before  any  visible  nuclear  changes.  Evidently  the  process  is  more 
than  ordinary  cell  division.  It  is  in  fact  an  agamic  reproduction 
comparable  to  this  form  of  reproduction  in  the  multicellular  forms, 
and  as  such  it  exhibits  characteristic  features  for  each  species  and 
involves  much  more  extensive  reconstitutional  changes  than  cell 
division. 

The  data  presented  in  chap,  v  and  in  the  preceding  sections  of 
the  present  chapter  demonstrate  that  in  at  least  many  of  the  meta- 
zoa  a  relation  exists  between  reconstitution  and  rejuvenescence. 
That  being  the  case,  the  extensive  reconstitutional  changes  involved 
in  fission  in  the  ciUates  make  it  at  least  probable  that  fission  brings 
about  a  greater  or  less  degree  of  rejuvenescence.  With  this  idea 
in  mind,  the  attempt  has  been  made  to  determine  whether  appre- 
ciable changes  in  susceptibility  occur  in  connection  with  fission  in 
the  ciliates.  The  forms  tested  thus  far  are  Paramecium,  Slcntor 
coeruleus,  a  small  form  of  Colpidium,  and  Urocentrum  turbo,  and  the 
results  are  essentially  the  same  for  all.  The  tests  were  made  upon 
actively  dividing  cultures  reared  from  sterile  infusions  inoculated 
with  a  few  individuals.  The  rearing  of  pure  line  cultures  was  not 
attempted,  because  definite  results  were  obtained  without  this 
procedure. 

In  the  early  stages  of  fission  no  appreciable  increase  in  suscepti- 
bihty  to  cyanide  has  been  observed.  If  any  exists,  it  is  not  sufii- 
ciently  great  to  appear  clearly  in  comparison  with  individual 
differences  in  susceptibility.  In  pure  line  cultures  some  increase 
in  susceptibility  in  the  earlier  stages  of  fission  might  perhaps  be 
demonstrated.  In  the  later  stages  of  fission,  however,  when  the 
two  daughter  individuals  are  approaching  separation  and  the  recon- 
stitutional changes  are  advanced,  the  susceptibility  is  distinctly 
greater  than  in  the  single  animals  of  approximately  the  same  size 
as  the  two  members  of  the  pair  together.     The  possibility  that  the 


142         .  SENESCENCE  AND  REJUVENESCENCE 

dividing  pairs  and  the  single  animals  belong  to  different  races  which 
differ  in  susceptibility  cannot  of  course  be  excluded  in  individual 
cases  except  in  pure  line  cultures,  but  the  uniformity  of  the  results 
obtained  with  large  numbers  of  individuals  and  in  repeated  tests 
render  this  possibility  negligible. 

But  the  susceptibility  is  highest  after  fission  is  completed.  In 
all  cases  the  smaller  individuals  are  in  general  very  clearly  more 
susceptible  than  the  larger.  This  difference  is  not  a  matter  of 
size  or  of  the  relation  between  surface  and  volume,  for  the  ciUa  and 
the  whole  body-surface  show  it.  The  cilia  and  ectoplasm  of  the 
larger  animals  are  in  general  much  less  susceptible  to  a  given  con- 
centration of  cyanide  than  those  of  the  smaller  animals.  As  death 
and  disintegration  proceed  in  a  lot  consisting  of  hundreds  or  thou- 
sands of  individuals,  it  soon  becomes  very  evident  that  the  smaller 
animals  are  dying  earlier  than  the  larger.  In  a  culture  of  Colpidium, 
for  example,  where  division  was  proceeding  very  rapidly,  animals 
below  a  certain  size  were  more  than  twice  as  numerous  as  those 
above  this  size,  but  after  deaths  began  to  occur  in  cyanide,  the 
smaller  animals  became  less  than  half  as  numerous  as  the  larger, 
and  still  later  only  about  one  small  to  five  large  was  found  alive. 
Similar  results  were  obtained  with  the  other  species.  In  a  Stentor 
culture  where  divisions  were  occurring  only  in  the  animals  of 
medium  size  or  above,  the  susceptibiHty  of  the  animals  below 
medium  size  was  much  greater  than  that  of  the  larger  animals. 
Some  of  the  smaller  animals  in  these  cultures  may  conceivably 
have  belonged  to  small  races  possessing  a  greater  susceptibiHty  at 
all  stages  than  the  large,  but  as  the  culture  was  increasing  rapidly 
in  numbers,  most  of  them  were  certainly  the  products  of  recent 
fission. 

These  data  are  in  complete  agreement  with  those  obtained 
from  the  study  of  the  flatworms  and  indicate  very  clearly  that  an 
increase  in  rate  of  metabolism  is  associated  with  the  process  of 
fission  in  the  cihate  infusoria  and  that  the  rate  of  metaboUsm  is 
highest  soon  after  fission.  In  other  words,  after  fission  the 
animals  are  physiologically  younger  than  before  fission,  and  in 
the  interval  between  two  fissions  they  undergo  some  degree  of 
senescence. 


AGAMIC  REPRODUCTION  AND  REJUVENESCENCE        143 

These  changes,  however,  are  apparently  not  the  only  factors 
concerned  in  preventing  progressive  race  senescence.  In  a  recent 
paper  Woodruff  and  Erdmann  ('14)  have  described  periodic  changes 
of  another  sort  which  they  call  "endomixis"  and  which  they  believe 
to  be  the  essential  factors  in  preventing  race  senescence.  These 
changes  consist  in  the  gradual  fragmentation,  degeneration,  and 
disappearance  of  the  meganucleus,  at  least  two  divisions  of  the 
micronuclei,  degeneration  of  some  of  the  micronuclei  thus  produced, 
and  the  formation  of  new  meganuclei  from  others.  This  process 
of  endomixis  resembles  the  nuclear  changes  in  conjugation,  except 
that  the  third  micronuclear  division  of  conjugation  which  gives 
rise  to  the  migratory  and  stationary  micronuclei  apparently  does  not 
occur  here,  and  there  is  no  union  of  micronuclei  at  any  time.  Wood- 
ruff and  Erdmann  point  out  that  endomixis  is  in  certain  respects 
similar  to  parthenogenesis,  but  not  directly  comparable  with  the 
usual  forms  of  it.  The  occurrence  of  rhythms  of  growth  and  rate 
of  division  in  protozoan  cultures  has  been  recognized  by  Calkins, 
Woodruff,  and  various  other  investigators.  Periods  of  more  rapid 
and  less  rapid  growth  and  division  alternate  more  or  less  regularly 
in  the  history  of  cultures.  Woodruff  and  Erdmann  find  that  the 
process  of  endomixis  which  extends  over  some  nine  cell  generations 
is  coincident  with  the  period  of  lowest  rate  of  growth  and  division 
in  the  rhythms,  that  at  the  climax  of  the  process  division  is  greatly 
delayed,  and  that  with  the  beginning  of  dift'erentiation  of  the  new 
meganuclei  recovery  is  rapid.  They  conclude  that  a  causal  rela- 
tion exists  between  the  reorganization  process  and  the  rhythms. 

This  process  of  endomixis  occurs  in  diff'erent  races  of  Paramecium 
aurelia  and  in  P.  caudatum  also,  and  probably  in  other  ciliate 
infusoria.  Many  of  the  observations  of  earUer  authors  on  degenera- 
tive changes  and  abnormal  nuclear  conditions  undoubtedly  concern 
stages  of  endomixis. 

While  further  inv-estigation  is  necessary  to  determine  how  gen- 
erally this  process  occurs  and  to  what  extent  its  occurrence  may  be 
experimentally  controlled,  it  is  evident  that  the  rhythms  and  the 
process  of  endomixis  represent  a  senescence-rejuvenescence  periotl, 
and  we  must  inquire  what  factors  are  primarily  or  chieily  concerned 
in  this  periodicity.    I  believe  that  we  must  look,  to  the  meganucleus 


144  SENESCENCE  AND  REJUVENESCENCE 

for  the  answer  to  this  inquiry.  The  meganucleus  of  the  infusoria 
is  apparently  a  speciaHzed  vegetative  organ  of  the  cell  not  found  in 
the  same  form  in  other  cells,  although  Goldschmidt  ('05)  has 
attempted  to  show  that  all  animal  cells  are  physiologically  if  not 
morphologically  binucleate  and  that  a  distinction  between  vegeta- 
tive or  somatic  and  reproductive  nuclear  substance  must  be  made. 
Whether  or  not  we  accept  this  view,  the  meganucleus  is  evidently 
a  specialized  organ,  and  all  the  facts  indicate  that  it  plays  an  impor- 
tant role  in  the  metabolic  activity  of  the  cell.  In  the  process  of 
division  it  apparently  undergoes  no  great  degree  of  reorganization, 
but  is  merely  separated  into  two  parts  and  continues  to  grow.  If 
the  successive  divisions  of  the  meganucleus  do  not  balance  the 
progressive  changes  between  divisions,  it  will  necessarily  undergo 
progressive  senescence,  and  if  no  other  method  of  rejuvenescence 
occurs,  death  from  old  age  must  finally  result. 

This,  I  believe,  is  what  actually  occurs.  The  period  from  the 
low  point  of  one  rhythm  to  the  low  point  of  the  next  represents  the 
length  of  life  of  the  meganucleus  under  the  existing  conditions. 
As  the  meganucleus  undergoes  senescence  after  its  differentiation 
as  a  meganucleus,  the  rate  of  growth  and  division  decreases,  sooner 
or  later  the  meganucleus  begins  to  degenerate,  and  a  physiological 
relation  of  some  sort  undoubtedly  exists  between  these  changes 
and  the  micronuclear  divisions  which  occur.  In  other  words,  the 
process  of  endomixis  is  apparently  the  periodic  replacement  of  a 
part  which  has  grown  old  by  a  new,  young  part  and  is  therefore 
analogous  in  certain  respects  to  the  replacement  of  differentiated 
old  cells  by  young  in  the  multicellular  organism.  Like  such  cells, 
the  meganucleus  apparently  does  not  undergo  rejuvenescence  but 
dies  of  old  age  and  is  replaced  by  a  new  one. 

Further  investigation  will  probably  show  that  the  length  of 
time  between  two  successive  endomixes  may,  like  many  other 
senescence  periods,  be  altered  and  controlled  experimentally  to  a 
greater  or  less  extent.  It  is  in  fact  possible  that  under  certain  con- 
ditions the  degree  of  rejuvenescence  occurring  in  the  ordinary 
divisions  may  be  sufficient  to  maintain  the  race  without  progressive 
senescence  of  the  meganucleus  and  so  without  endomixis,  although 
it  may  be   that  the  rejuvenescence  in  division  is  rather  cyto- 


AGAMIC  REPRODUCTION  AND  REJUVENESCENCE        145 

plasmic  than  nuclear.  That  the  age  cycle  of  certain  flatworms  may 
be  altered  to  a  very  considerable  extent  by  experimental  nutritive 
and  other  conditions  will  be  shown  in  chap.  vii.  Moreover,  the 
different  behavior  of  different  races  as  regards  conjugation'  suggests 
that  internal  as  well  as  external  factors  will  be  found  to  play  a  part 
in  determining  the  periodicity. 

But  whatever  the  differences  resulting  from  race  or  environ- 
mental conditions,  the  occurrence  in  the  ciliates  of  some  degree  of 
senescence  in  each  generation  and  some  degree  of  rejuvenescence 
in  each  agamic  reproduction  and  the  occurrence  of  progressive 
senescence  in  the  meganucleus  ending  in  its  death  and  replacement 
by  a  new,  young  organ  demonstrate  that  these  unicellular  animals 
are  not  fundamentally  different  from  multicellular  forms.  They 
are  not,  as  Weismann  ('82)  believed,  immortal  because  they  do  not 
grow  old,  but  simply  as  other  organisms  are,  because  they  repro- 
duce and  undergo  reconstitution  during  reproduction  and  because 
old  organs  die  and  are  replaced  by  young. 

AGAMIC  REPRODUCTION  AND  REJUVENESCENCE  IN  COELENTERATES 

Among  the  coelenterates  only  the  fresh-water  hydra  and  one 
species  of  the  colonial  hydroids  have  been  tested  by  the  suscepti- 
bility method.  In  hydra  agamic  reproduction  is  a  process  of 
budding.  In  Hydra  j'usca  the  bud  arises  near  the  junction  of  the 
thicker  body  with  the  more  slender  stalk,  and  in  its  earlier  stages  is 
merely  a  rounded  outgrowth  including  both  ectodermal  and  cnto- 
dermal  layers  of  the  body- wall  (Fig.  48).  Cell  division  and  growth 
occur  rapidly  in  it,  it  elongates,  and  in  the  course  of  a  few  days 
tentacles  and  a  mouth  begin  to  develop  at  its  distal  end  (Fig.  49). 
Meanwhile  the  region  of  attachment  to  the  parent  body  gradually 
undergoes  constriction,  until  finally  the  new,  small  animal  separates 
from  the  parent,  falls  to  the  bottom,  attaches  itself,  and  begins 
to  lead  an  active  life.  In  this  process  a  portion  of  the  body-wall  of 
the  parent  has  undergone  reconstitution  into  a  new,  independent 
individual. 

A  comparison  of  the  susceptibility  to  cyanide  of  small  animals 
newly  developed  in  this  way  with  the  larger  parent  shows  that  the 

"Jennings,  '10,  '13;    Calkins  and  Gregory,  '13. 


146 


SENESCENCE  AND  REJUVENESCENCE 


newly  developed  individuals  are  distinctly  more  susceptible  than 
the  parents,  i.e.,  they  are  physiologically  younger.  In  the  earlier 
stages  of  the  bud,  however,  while  it  is  still  attached  to  the  parent 
body  and  before  it  has  developed  the  capacity  for  motor  activity, 
its  susceptibility  is  not  appreciably  different  from  that  of  adjoining 
regions  of  the  parent  body,  or  it  may  be  even  less  susceptible  than 
these  regions. 

The  fact  that  the  increased  susceptibility  appears  only  after 
the  asexually  produced  individual  is  separated  from  the  parent 


Figs.  48,  49. — Two  stages  in  the  development  of  a  bud  in  Hydra 

seems  at  first  glance  not  to  agree  fully  with  the  data  and  conclusions 
from  other  forms,  but  this  disagreement  is  only  apparent,  and  re- 
sults from  the  complication  of  the  results  by  the  factors  of  motor 
activity  and  food.  Motor  activity  of  an  individual,  or  even  of  a 
region  of  the  body  in  hydra,  increases  very  considerably  the  sus- 
ceptibility of  that  individual  or  region  to  cyanide.  It  is  very 
generally  the  case  that  the  animals  which  show  the  greater  motor 
activity  after  being  placed  in  cyanide  die  and  disintegrate  earlier 
than  the  less  active,  and  it  has  often  been  observed  that  marked 


AGAMIC  REPRODUCTION  AND  REJUVENESCENCE        147 

contraction  in  cyanide  of  a  particular  body  region  is  followed  by 
the  death  and  disintegration  of  that  region  before  other  parts. 
Evidently  motor  activity,  although  slow,  increases  the  rate  of 
metabolism  in  hydra  to  a  very  marked  degree.  This  is  perhaps  to 
be  expected  from  the  fact  that  the  motor  mechanism  in  this  organ- 
ism is  not  highly  developed,  but  is  merely  a  part  of  the  ectoderm 
cell.  Motor  activity  undoubtedly  involves  the  whole  cell  and  at 
least  all  the  cells  of  the  ectoderm  in  the  region  where  it  occurs.  To 
all  appearances  it  is  a  very  laborious  process,  and  even  after  the 
strongest  stimulation  it  is  relatively  slow  and  inefficient.  In  short, 
the  observations  made  by  the  susceptibility  method  indicate  that 
the  increased  metabolism  associated  with  motor  activity  is  relatively 
very  great. 

The  bud  in  the  early  stages  of  development  exhibits  very  little 
motor  activity,  and  movement  does  not  attain  its  maximum  until 
separation  from  the  parent  takes  place.  The  result  of  this  differ- 
ence in  motor  activity  between  bud  and  parent  is  that,  even  though 
growth  and  development  are  proceeding  more  rapidly  in  the  bud 
than  in  the  parent,  the  rate  of  metabolism  is  not  greater  in  the 
bud  where  motor  activity  is  slight  than  in  the  parent  where  it  is 
much  greater.  But  as  soon  as  the  bud  becomes  independent, 
its  motor  activity  is  comparable  with,  perhaps  even  greater 
than,  that  of  the  parent,  and  then  its  susceptibihty  to  cyanide 
is  distinctly  greater,  i.e.,  its  rate  of  metabolism  is  higher  than 
that  of  the  parent. 

Moreover,  the  young  bud  while  still  attached  to  the  parent 
grows  at  the  expense  of  food  ingested  by  the  parent  body,  rather 
than  at  the  expense  of  its  own  tissues.  It  does  not  undergo  reduc- 
tion, but  grows  during  its  reconstitution  from  a  part  of  the  parent 
body  into  a  new  individual.  Since  rejuvenescence  is  undoubtedly 
associated  with  reduction,  as  the  following  chapter  will  show,  the 
bud,  which  receives  food  and  grows  rapidly  throughout  its  devel- 
opment, does  not  become  as  young  physiologically  at  any  stage  as 
if  its  development  occurred  at  the  expense  of  its  own  tissues. 

In  the  marine  hydroid  Pennaria  tiarella,  agamic  buds  are  j)ro- 
duced  as  in  hydra  but  remain  perrnanently  in  connection  with  the 
parent  stem  or  branch,  so  that  a  branching  tree-like  colony  with  the 


148 


SENESCENCE  AND  REJUVENESCENCE 


zooids  or  hydranths  at  the  tips  of  the  branches  results.     Fig.  50 
shows  a  portion  of  such  a  Pennaria  colony.     In  this  species  the  new 


Figs.  50-52. — Pennaria  tiareUa:  Fig.  50,  part  of  a  colony,  including  a  large, 
old  hydranth,  //,  bearing  a  medusa  bud,  m,  a  younger  hydranth,  h',  and  a  hydranth 
bud,  h";  Figs.  51,  52,  developmental  stages  of  hydranth. 

hydranth  bud  arises  laterally  a  short  distance  below  the  terminal 
hydranth  of  a  stem  or  branch  (Fig.  50,  //')•     It  is  an  outgrowth 


AGAMIC  REPRODUCTION  AND  REJUVENESCENCE        149 

including  both  layers  of  the  bod}--\vall,  as  in  hydra,  and  in  its  earlier 
stages  is  rounded  in  form  and  inclosed  in  the  chitin<jus  perisarc 
which  covers  the  stem.  As  development  proceeds,  it  emerges  from 
the  perisarc,  undergoes  elongation,  and  the  tentacles  begin  to  appear, 
as  indicated  in  Fig.  51.  A  later  stage  of  development  is  shown  in 
Fig.  52,  a  fully  developed  hydranth  in  Fig.  50,  //',  and  an  old 
hydranth  bearing  a  medusa  bud,  m,  in  Fig.  50,  //.  The  agamic 
production  of  hydranths  in  this  form  is  then  a  reconstitution  of  a 
portion  of  the  stem  into  a  new  hydranth. 

As  regards  the  susceptibility  of  the  different  stages,  both  motor 
activity,  as  in  hydra,  and  the  presence  of  the  chitinous  perisarc 
contribute  to  obscure  the  changes  in  susceptibility  associated  with 
the  reconstitution  of  stem  into  hydranth.  The  susceptibilitv  of 
the  early  stages  of  hydranth  development,  such  as  //"  in  Fig.  50, 
cannot  be  compared  directly  with  that  of  stages  like  Figs.  51  and 
52,  because  these  early  stages  are  inclosed  like  the  stem  in  the 
chitinous  perisarc,  while  in  the  later  stages  the  hydranth  is  naked. 
Neither  are  these  early  stages  directly  comparable  with  such  stages 
as  Fig.  50,  h  or  //',  for  in  the  former  motor  activity  is  absent,  while 
in  the  latter  it  is  fully  developed.  It  is  possible,  however,  to  com- 
pare the  susceptibility  of  such  a  stage  as  Fig.  50,  //',  with  that  of 
adjoining  regions  of  the  stem,  for  both  are  inclosed  in  perisarc,  and 
a  comparison  of  this  sort  shows  that  the  early  bud  is  in  general 
distinctly  more  susceptible,  i.e.,  it  possesses  a  higher  rate  of  metab- 
olism and  is  physiologically  younger  than  the  stem  adjoining  it. 
But  in  this  case,  as  in  hydra,  the  increase  in  rate  connected  with 
the  formation  of  a  new  individual  is  less  than  it  would  be  if  the 
region  were  physiologically  isolated  and  underwent  development 
at  the  expense  of  its  own  tissues  rather  than  of  nutritive  material. 
As  it  is,  the  bud  has  abundant  food  and  grows  during  development, 
while  the  isolated  piece  undergoes  reduction. 

In  the  later  stages  of  development  the  perisarc  no  longer  enters 
as  a  factor,  but  differences  in  motor  activity  still  e.\ist  between 
different  stages.  At  the  stage  shown  in  Fig.  51  motor  activity  is 
absent  or  inappreciable,  but  the  susceptibility  of  this  stage  is 
nevertheless  usually  somewhat  greater  than  that  of  an  old  hydranth. 
like  h  in  Fig.  50,  and  less  than  that  of  a  younger  hydranth,  like 


I50  SENESCENCE  AND  REJUVENESCENCE 

//  in  Fig.  50.  At  the  stage  of  Fig.  52  motor  activity  is  present  to 
some  extent,  though  much  less  than  in  still  later  stages.  This 
stage  is  distinctly  more  susceptible  than  such  hydranths  as  h  in 
Fig.  50.  Here,  where  motor  activity  has  begun  to  appear,  even 
though  it  is  still  slight,  the  difference  in  physiological  condition 
between  morphologically  young  and  old  hydranths  becomes  dis- 
tinctly evident.  From  this  stage  on  the  susceptibility  decreases 
as  development  proceeds,  but  it  does  not  attain  a  constant  level 
even  after  the  morphological  form  of  the  hydranth  is  fully  devel- 
oped. On  a  stem  like  that  shown  in  Fig.  50,  for  example,  the 
hydranth  //,  which  is  younger  in  point  of  time  than  the  terminal 
hydranth  h,  shows  in  general  a  higher  susceptibihty,  i.e.,  is  physio- 
logically younger  than  the  latter.  In  spite  then  of  the  presence 
of  the  perisarc  in  certain  stages  and  the  differences  in  motor  activity 
in  other  stages,  the  dififerences  in  susceptibility  indicate  that  a 
certain  degree  of  rejuvenescence  is  associated  with  the  agamic 
reproduction  of  hydranths  in  Pennaria.  It  is  still  a  question, 
however,  to  what  extent  new  parts  which  arise  by  budding  in 
hydroids  are  formed  by  dedifferentiation  and  redifferentiation  of 
old  cells  and  to  what  extent  by  the  interstitial  cells  which  are  small 
cells  lying  in  groups  between  the  other  cells  of  the  body-wall  and 
which  are  commonly  regarded  as  embryonic  reserve  cells.  From 
this  point  of  view  the  apparent  rejuvenescence  which  occurs  in 
connection  with  budding  might  be  regarded  as  simply  a  replace- 
ment of  the  older  differentiated  cells  by  the  younger,  undiffer- 
entiated. Doubtless  the  interstitial  cells  are  less  highly  specialized 
than  various  other  cells  and  so  react  more  readily  to  the  change 
in  conditions,  but  the  very  fact  that  they  were  inactive  before  and 
became  active  in  the  development  of  the  bud  indicates  a  change  in 
their  physiological  condition  in  the  direction  of  a  higher  rate  of 
metabolism.  Moreover,  there  is  every  indication  that  at  least 
many  of  the  specialized  cells  of  the  body-wall  do  take  part  in  bud- 
formation  and  actually  undergo  more  or  less  dedifferentiation. 

In  addition  to  the  asexual  production  of  hydranths,  Pennaria  also 
gives  rise  asexually  to  medusa  buds,  which  do  not  usually,  however, 
develop  into  free-swimming  medusae  but  remain  attached  to  the 
parent  body.     These  appear  on  the  body  of  the  hydranth  im- 


AGAMIC  REPRODUCTION  AND  REJUVENESCENCE        151 

mediately  distal  to  the  circle  of  proximal  tentacles  '{m,  Fig.  50) . 
Three  stages  of  development  of  the  medusa  bud  drawn  to  the 
same  scale  are  shown  in  Figs.  53-55.  In  the  early  stages  the 
medusa  bud  is  always  more  susceptible  to  cyanide  than  the  adjoin- 
ing regions  of  the  hydranth  from  which  it  arose,  and  its  suscepti- 
bility decreases  as  development  proceeds,  the  large,  fully  developed 
bud  being  much  less  susceptible  than  the  adjoining  regions  of  the 
parent  hydranth.  These  differences  in  susceptibility  are  not 
dependent  upon  differences  in  size,  for  they  concern  primarily 
the  surface  of  the  body.  Differences  in  motor  activity  may  be 
concerned  in  the  difference  in  susceptibility  between  the  fully 
developed  medusa  bud  and  the  hydranth,  but  the  greater  suscep- 
tibility of  the  bud  in  early  stages  as  compared  with  the  hydranth 
cannot  be  accounted  for  in  this  way,  for  motor  activity  is  present 


43  54 

'  55 

Figs.  53-55. — Pennaria  Harella:   three  stages  in  the  development  of  a  medusa  bud 

in  the  hydranth  but  not  in  the  medusa  bud.  Evidently  the 
medusa  bud  in  early  stages  is  physiologically  younger  than  the 
region  of  the  hydranth  from  which  it  arises. 

But  the  susceptibility  of  young  medusa  buds  is  in  general 
distinctly  less  than  that  of  young  hydranths  of  the  stage  of  Figs. 
51  and  52,  after  emergence  from  the  perisarc.  That  is,  the  young 
medusa  bud  is  not  as  young  as  the  young  hydranth.  The  medusa 
bud  arises  from  a  more  highly  specialized  region  of  the  colony  than 
the  hydranth  bud  and  develops  into  a  more  highly  specialized 
zooid  or  individual.  Apparently  the  reconstitution  of  a  portion 
of  the  hydranth  body  into  a  medusa  bud  does  not  carry  the  region 
concerned  back  to  so  early  a  physiological  stage  as  that  attained 
in  the  reconstitution  of  a  region  of  the  stem  into  a  young  hytlranth. 
This  difference  in  physiological  condition  between  hydranth  bud 
and  medusa  bud  is  probably  the  dynamic  basis,  or  at  least  the 


152  SENESCENCE  AND  REJUVENESCENCE 

dynamic  correlate,  of  the  difference  in  morphological  development. 
In  this  connection  it  is  also  of  interest  to  note  that  in  Pennaria 
medusa  buds  appear  only  upon  hydranths  which  are  physiologically 
relatively  old,  while  the  hydranth  buds  usually  arise  on  the  physi- 
ologically younger  regions  of  the  stem.  In  other  species  of  hydroids, 
where  the  growth  form  is  different,  the  physiological  relations  may 
also  prove  to  be  more  or  less  widely  different,  although  medusa  buds 
in  general  arise  in  connection  with  a  fully  developed  hydranth,  or 
a  highly  specialized  reproductive  zooid  or  from  an  apparently 
specialized  region  of  the  stem  just  proximal  to  a  hydranth,  while 
hydranth  buds  arise  from  less  highly  specialized  regions.  It  is 
probable  that  where  such  complicating  factors  as  presence  of  the 
perisarc  or  differences  in  motor  activity  do  not  obscure  the  differ- 
ences in  susceptibility  associated  with  physiological  age,  similar 
differences  between  the  different  forms  of  agamic  reproduction 
will  be  found  in  other  species. 

To  sum  up,  the  susceptibility  method  indicates  not  only  that  a 
considerable  degree  of  rejuvenescence  is  associated  with  agamic 
reproduction  in  Pennaria  but  also  that  different  stages  of  rejuvenes- 
cence are  represented  in  the  different  forms  of  agamic  reproduction 
in  this  species.  In  the  more  specialized  reproductive  process  the 
young  stages  are  apparently  somewhat  older  physiologically  than 
in  the  less  specialized  process. 

REFERENCES 

Baitsell,  G.  a. 

191 2.     "Experiments  on  the  Reproduction  of  Hypotrichous  Infusoria: 

I,  Conjugation  between  Closely  Related  Individuals  in  Stylonychia 

pustulata,"  Jour,  of  Exp.  Zool.,  XIII. 
1914.     "Experiments,  etc.:    II,  A  Study  of  the  So-called  Life  Cycle  in 

Oxytricha  fallax  and  Pleurotricha  lanceolate,"  Jour,  of  Exp.  Zool., 

XVI. 

Calkins,  G.  N. 

1902a.  "Studies  on  the  Life-History  of  Protozoa:   I,  The  Life  Cycle  of 

Paramecium  caudatum,"  Arch.  f.  Entwickelungsmech.,  XV. 
19026.  "Studies,  etc.:   Ill,  The  Six  Hundred  and  Twentieth  Generation 

of  Paramecium,'"  Biol.  Bull.,  III. 
1904.     "Studies,  etc.:  IV,  Death  of  the  A-Series:    Conclusions,"  Jotir. 

of  Exp.  Zool.,  I. 


AGAMIC  REPRODUCTION  AND  REJUVENESCENCE         i  53 

Calkins,  G.  N.,  and  Gregory,  L.  H. 

1913.  "Variations  in  the  Progeny  of  a  Single  Ex-Conjugant  of  Para- 
mecium  caudatum,"  Jour,  of  Exp.  ZooL,  XV. 

Child,  C.  M. 

1910.     "Physiological  Isolation  of  Parts  and  Fission  in  Planaria,''  Arch. 

f.  Entwickclungsmech.,  XXX  (Festbd.  f.  Roux),  II.  Tcil. 
191  i(Z.  "Die  physiologische  Isolation  von  Teilen  des  Organismus,"  Vorlr. 

und  Aiifs.  ii.  Entwickclungsmech.,  XI. 
19116.   "Studies  on  the  Dynamics  of  Morphogenesis  and  Inheritance  in 

Experimental  Reproduction:    I,  The  Axial  Gradient  in  Phmaria 

dorotoccphala  as  a  Limiting  Factor  in  Regulation,"  Jour,  of  Exp. 

ZooL,  X. 
191  ic.   "Studies,  etc.:    Ill,  The  Formation  of  New  Zooids  in  Planaria 

and  Other  Forms,"  Jour,  of  Exp.  ZooL,  XI. 

191 2.  "Studies,  etc.:  IV,  Certain  Dynamic  Factors  in  the  Regulatory 
Morphogenesis  of  Phmaria  dorotoccphala  in  Relation  to  the  .\xial 
Gradient,"  Jour,  of  Exp.  ZooL,  XIII. 

19130.  "Studies,  etc.:  VI,  The  Nature  of  the  Axial  Gradients  in  Planaria 
and  Their  Relation  to  Antero-posterior  Dominance,  Polarity 
and  Symmetry,"  Arch.  f.  Entwickelungsmech.,  XXXVII. 

19136.  "The  Asexual  Cycle  in  Planaria  vclata  in  Relation  to  Senescence 
and  Rejuvenescence,"  Biol.  Bull.,  XXV. 

1914.  Asexual  Breeding  and  Prevention  of  Senescence  in  Planaria 
velata,"  BioL  Bull.,  XXVI. 

Enriques,  p. 

1903.  "Sulla  cosi  detta'  degenerazione  senile'  dei  protozoi,"  Monilore 
ZooL  ItaL,  XIV. 

1907.  "La  conjugazione  e  il  difTerenziamento  sessuale  negli  Infusori," 
Arch.f.  Protistcnkunde,  IX. 

1908.  "Die  Konjugation  und  sexuelle  Differenzierung  der  Infusorien," 
Arch.  f.  Protistcnkunde,  XII. 

GOLDSCHMIDT,  R. 

1905.  "Der  Chromidialapparat  lebhaft  funktionicrender  Gewebszellen," 
ZooL  Jahrbucher;  Abt.  f.  Anat.  u.  Ont.,  XXL 

Jennings,  H.  S. 

1910.  "What  Conditions  Induce  Conjugation  in  Paramecium T'  Jour. 
of  Exp.  ZooL,  IX. 

1913.  "The  Effect  of  Conjugation  in  Paramecium,"  Jour,  of  Exp.  ZooL, 
XIV. 

Jennings,  H.  S.,  and  Hargitt,  G.  T. 

1910.  "Characteristics  of  the  Diverse  Races  of  Paramecium,"  Jour,  of 
MorphoL,  XXL 


154  SENESCENCE  AND  REJUVENESCENCE 

Johnson,  H.  P. 

1893.     "A  Contribution  to  the  INIorphology  and  Biology  of  the  Stentors," 
Jour,  of  MorphoL,  VIII. 

Ma  UPAS,  E. 

1888.  "Recherches  experimentales  sur  la  multiplication  des  Infusories 
cilies,"  Arch,  de  zool.  exp.,  (2),  VI. 

1889.  "La  rajeunissement  karyogamique  chez  les  cilies,"  Arch,  de  zool. 
exp.,  (2),  VII. 

Weismann,  a. 

1882.     iiber  die  Dauer  des  Lebens.    Jena. 

Woodruff,  L.  L. 

1908.  "The  Life-Cycle  of  Paramecium  When  Subjected  to  a  Varied 
Environment,"  Am.  Nat.,  XLII. 

1909.  "Further  Studies  on  the  Life-Cycle  of  Paramecium,"  Biol.  Bull., 
XVII. 

1911a.  "Two  Thousand  Generations  of  Paramecium,"  Arch.f.  Protisten- 

kunde,  XXI. 
191 16.  ''Paramecium    aurelia    and    Paramecium    caudatum,"    Jour,    of 

MorphoL,  XXII. 
1913a.  "Dreitausand  und   dreihundert   Generationen   von   Paramecium 

ohne    Konjugation   oder   kiinstliche    Reizung,"    Biol.  Centralbl., 

XXXIII. 
1913&.  "Cell  Size,  Nuclear  Size  and  the  Nucleo-cytoplasmic  Relation 

during  the  Life  of  a  Pedigreed  Race  of  Oxytricha  fallax,"  Jour. 

of  Exp.  Zool.,  XY. 
1914.     "On  So-called  Conjugating  and  Non-conjugating  Races  of  Para- 
mecium," Jour,  of  Exp.  Zool.,  XVI. 
Woodruff,  L.  L.,  and  Erdmann,  Rhoda. 

1914.     "A  Normal  Periodic  Reorganization  Process  without  Cell  Fusion 

in  Paramecium,"  Jour,  of  Exp.  Zool.,  XVII. 
ZwEiBAUM,  J.  (Enriques  et  Zweibaum)  . 

191 2.     "La  conjugaison  et  la  differenciation  sexuelle  chez  les  Infusories: 

V,  Les  conditions  necessaires  et  suffisantes  pour  la  conjugaison  du 

Paramoecium  caudatum,"  Arch.  f.  Protistenkunde,  XXVI. 


CHAPTER  VII 

THE  ROLE  OF  NUTRITION  IN  SENESCENCE  AND  REJUVENES- 
CENCE IN  PLANARIA 

REDUCTION  BY  STARVATION  IN  Plauaria 

The  various  species  of  Planar ia  are  capable  of  living  for  months 
without  food  from  external  sources.  During  such  periods  of 
starvation,  however,  they  undergo  reduction  in  size,  many  cells 
degenerate,  and  some  organs  may  completely  disappear.  Various 
investigators,  among  them  F.  R.  Lillie,  'oo;  Schultz,  '04;  Stoppen- 
brink,  '05,  have  considered  one  phase  or  another  of  this  process  of 
reduction,  and  Lillie  and  Schultz  particularly  have  called  attention 
to  the  fact  that  in  its  proportions  and  chief  morphological  charac- 
teristics the  animal  reduced  by  starvation  resembles  the  young 
animal  and  have  pointed  out  that  the  changes  which  occur  during 
reduction  indicate  that  the  process  of  development  is  reversible. 
In  an  earlier  chapter  (p.  57)  I  have  suggested  that  it  is  preferable 
to  use  the  term  "  regressibility "  rather  than  reversibility  for  such 
changes,  since  the  occurrence  of  reduction  or  dedifferentiation  in  an 
organism  does  not  necessarily  imply  a  reversal  of  the  reactions  con- 
cerned in  progressive  development.  Only  from  the  morphological 
viewpoint  are  we  justified  in  speaking  of  a  reversal  of  development. 

The  reduction  in  size  of  Plauaria  during  starvation  is  unques- 
tionably due  to  the  re-entrance  of  its  structural  material  into 
metabolism  as  a  source  of  energy.  Schultz  finds  that  reduction 
in  Plauaria  is  due  to  the  disappearance  of  whole  cells  and  organs 
rather  than  to  decrease  in  size  of  the  cells  in  general.  This  is  un- 
doubtedly true  to  a  large  extent,  but  my  own  unpublished  observa- 
tions indicate  that  some  decrease  in  size  does  occur  in  at  least  many 
cells  in  the  starving  planarian,  and  other  authors  who  have  investi- 
gated the  cellular  changes  in  animals  during  starvation  have  reached 
similar  conclusions.' 

'The  following  references  constitute  a  partial  bibliography  of  the  subject: 
Kasanzefifj  '01,  and  Wallengren,  '02,  found  marked  reduction  in  the  size  of  Paramecium 
during  hunger.     Citron,  '02,  observed  decrease  in  size  of  ectoderm  cells  in  a  coclcntcratc 


'3D 


156  SENESCENCE  AND  REJUVENESCENCE 

In  the  course  of  observations  on  Planaria  dorotocephala  I  have 
found  that  the  lower  Hmit  of  reduction  differs  rather  widely  accord- 
ing to  the  original  size  of  the  animal.  Animals  of  twenty-five 
millimeters  in  length  before  starvation  begin  to  die  when  they  are 
reduced  to  a  length  of  five  or  six  millimeters,  while  animals  which 
are  six  or  seven  millimeters  in  length  before  starvation  may  undergo 
reduction  to  a  length  of  one  or  two  millimeters  before  death. 
As  I  have  suggested  elsewhere,  death  in  these  cases  is  probably  not 
due  to  lack  of  available  material,  for  pieces  isolated  from  starving 
animals  are  capable  of  reconstitution  to  whole  animals  and  may  then 
undergo  reduction  to  a  much  smaller  size  before  death.  Death, 
at  least  in  the  larger  animals  reduced  by  starvation,  is  probably  due 
to  altered  correlative  conditions  resulting  from  changes  in  the 
axial  gradient  in  rate  of  metabolism  (Child,  '14,  p.  443). 

In  consequence  of  their  ability  to  undergo  extreme  reduction 
before  death  occurs  from  starvation  the  planarians  would  consti- 
tute valuable  material  for  the  study  of  physiological  and  particu- 
larly of  metabolic  changes  connected  with  inanition  if  it  were  not 
for  their  small  size.  But  now  with  the  Tashiro  biometer  and  with 
the  susceptibility  method  we  are  able  to  obtain  some  light  on  at 
least  certain  features  of  the  metabolism  in  these  starving  animals. 
Some  of  the  data  bearing  upon  this  problem  are  presented  in  the 
following  section. 

CHANGES  IN   SUSCEPTIBILITY   DURING   STARVATION   IN 

Planaria  dorotocephala  and  P.  velata 

Since  the  animals  reduced  by  starvation  resemble  young  animals 
morphologically,  the  question  whether  they  are  young  physio- 
logically at  once  suggests  itself.  If  the  reduced  animals  are  fed, 
growth  begins  again,  and  the  animals  are  not  only  indistinguishable 
from  young,  growing  animals  in  appearance  and  behavior,  but  are 
able  to  go  through  the  life  history  again  from  the  stage  at  which 
feeding  began.     Moreover,  the  reduced  animals  are  very  active 

during  starvation.  In  the  higher  animals  decrease  in  size  of  gland  cells,  muscle  cells, 
and  nerve  cells  during  starvation  has  been  recorded  by  various  authors,  among 
whom  are  Heumann,  '50;  Rindfleisch,  '68;  Morpurgo,  '88,  '89;  Downerowitsch,  '92; 
Statkewitsch,  '94;   Lukjanow,  '97;   Morgulis,  '11. 


NUTRITIOX  IX  SENESCENCE  AND  REJUVENESCENCE     157 

and  highly  irritable,  reacting  strongly  and  rapidly  to  various  kinds 
of  stimuli.  Slight  movements  of  the  water  or  a  slight  jarring  uf 
the  aquarium,  to  which  well-fed,  old  worms  do  not  respond  at  all, 
will  bring  them  into  active  movement,  and  when  wounded  or  when 
the  body  is  cut  in  two  they  react  much  more  strongly  than  old 
worms.  In  all  these  respects  they  resemble  young  rather  than  old 
animals.  In  fact,  their  general  behavior  indicates  very  clearly 
that  they  have  become  physiologically  young  during  the  course  ol 
reduction.  But  with  the  aid  of  the  susceptibility  method  it  is 
possible  to  obtain  more  positive  knowledge  upon  this  point. 

The  comparative  susceptibility  of  starving  animals  may  be 
determined  in  two  ways:  when  temperature  and  other  external 
conditions  are  controlled,  the  susceptibilities  of  a  uniform  stock  at 
different  stages  of  starvation  may  be  directly  compared  with  each 
other.  This  method  of  procedure  will  show  directly  whether  the 
susceptibiUty  increases,  decreases,  or  remains  constant  during 
starvation.  On  the  other  hand,  the  susceptibility  of  animals  at 
any  stage  of  starvation  may  be  compared  with  that  of  fed  animals 
of  the  same  size  or  of  animals  of  the  original  size  and  condition  of 
the  stock  before  starvation.  In  this  way  also  changes  in  suscepti- 
bility may  be  determined.  Records  of  experiments  of  both  sorts 
are  given  below. 

In  Table  II  the  decrease  in  length  and  increase  in  susceptibilit)-, 
determined  at  intervals  of  about  two  weeks  during  three  months  of 

TABLE  II 


Length  of  Starvation 
Period  in  Days 

Length  of  Animals  in 
Millimeters 

Survival  Time  of  Ten 

Animals  in  KCN 

o.ooi  Mol. 

Mean  Siir\'ival  Time 

0 

15-18 

15-17 

10-12 

9-10 

7-  8 

5 

3-5-4 

6''30">-9''00" 
6''oo"'-7''oo'" 
5'>oo"-6''30™ 

^hQQm.-hQQin 
2liQQm_^hQQin 

2''oo"^3''3o"' 

jh2Qm_2h^Qm 

7''45'" 

14 

•?2 

5''45" 

4; 

4'' 50" 

60 

77 

91 ■••• 

starvation,  are  recorded.  The  first  two  columns  of  the  table  are 
self-explanatory;  in  the  third  column  the  times  given  are  the  times 
of  complete  disintegration  of  the  first  and  last  of  the  worms  of  each 


158  SENESCENCE  AND  REJUVENESCENCE 

lot  of  ten  worms,  i.e.,  this  column  gives  the  extremes  of  the  survival 
times  and  the  fourth  column  the  means.  The  table  shows  at  a 
glance  that  the  susceptibility  of  the  animals  increases  very  greatly 
during  the  course  of  starvation,  the  mean  survival  time  decreasing 
from  seven  hours  and  forty-five  minutes  in  the  large,  well-fed 
animals  at  the  beginning  of  the  starvation  period  to  two  hours  in 
the  reduced  animals  after  ninety-one  days  of  starvation. 

The  changes  in  susceptibility  have  been  determined  in  the  same 
way  for  several  other  starvation  stocks,  some  made  up  from  larger 
animals  than  these,  others  from  smaller,  and  still  others  from  ani- 
mals of  the  same  size.  Different  stocks  were  kept  during  starva- 
tion under  various  conditions  of  temperature,  light,  aeration,  and 
change  of  water,  but  in  all  essentially  the  same  result  was  obtained, 
viz.,  a  great  and,  except  for  slight  irregularities  in  a  few  cases  which 
were  evidently  due  to  incidental  uncontrolled  factors,  a  continuous 
increase  in  susceptibihty  during  starvation. 

According  to  the  second  method  of  procedure  mentioned  above, 
the  susceptibility  of  the  starved  animals  may  be  compared  directly 
with  that  of  fed  animals.  The  records  of  two  tests  of  this  sort 
are  presented. 

In  the  first  of  these  several  hundred  worms  fifteen  to  eighteen 
millimeters  long  were  selected  from  freshly  collected  material  as  a 
starvation  stock.  After  eighty-one  days  of  starvation  the  animals 
were  reduced  to  a  length  of  seven  to  eight  millimeters,  and  the 
susceptibility  of  ten  of  the  reduced  worms  is  shown  in  the  curve  cd 
of  Fig.  56.  For  comparison  the  susceptibility  curves  of  ten  ani- 
mals of  the  same  size  and  condition  as  the  members  of  the  starva- 
tion stock  before  reduction  {ej,  Fig.  56)  and  of  ten  well-fed,  young 
animals  of  the  same  size  as  the  animals  reduced  by  starvation  {ah, 
Fig.  56)  are  given.  The  young,  fed  animals  are  most,  the  old, 
fed  animals  the  least,  susceptible,  but  the  susceptibihty  of  the 
animals  reduced  by  starvation  is  much  nearer  that  of  the  young 
animals  than  that  of  the  old  and  therefore  must  have  undergone 
marked  increase  during  reduction. 

In  another  case  the  starvation  stock  was  composed  of  animals 
twenty  to  twenty-four  millimeters  long,  and  the  determination  of 
susceptibilities  recorded  in  Fig.  57  was  made  after  ninety  days  of 


NUTRITION  IN  SENESCENCE  AND  REJUVENESCENCE      159 


complete  starvation  in  filtered  water.  The  curve  ab,  drawn  as  an 
unbroken  line  in  Fig.  57,  is  the  susceptibility  curve  of  ten  starved 
animals  which  have  undergone  reduction  to  a  length  of  seven  to 
eight  millimeters.  The  second  curve  ab,  drawn  as  a  broken  line, 
shows  the  susceptibility  of  ten  newly  collected,  young,  growing 
animals  of  the  same  size  as  the  reduced  worms.  A  part  of  the 
original  stock  was  fed,  while  the  others  were  starved,  and  the  curve 


Stages    ■ • 


II 


III 


IV 


Hours  I  234567 

Fig.  56. — Susceptibility  of  Planaria  dorotocephala  to  KCX  o.ooi  tnol.  in  relation 
to  nutritive  condition  and  age:  ab,  susceptibility  of  well-fed,  growing  animals  7-8 
mm.  in  length;  cd,  susceptibility  of  animals  reduced  by  starvation  from  15-18  mm 
to  7-8  mm.;  ef,  susceptibility  of  well-fed  animals  15-18  mm.  in  length. 

cd  shows  the  susceptibility  of  these  animals.  During  the  three 
months  of  feeding  these  worms  have  of  course  grown  somewhat 
older,  but  in  full-grown  animals  like  these  the  change  in  three 
months  is  slight.  But  the  susceptibility  of  the  starving  animals 
has  increased  until  it  is  about  the  same  as  that  of  young,  growing 
animals  of  the  same  size. 

Determinations  of  susceptibiHty  by  the  direct  method  with 
cyanide,  alcohol,  and  ether  as  reagent  have  been  made  on  several 


i6o 


SENESCENCE  AND  REJUVENESCENCE 


hundred  individuals  of  Planaria  dorotocephala  in  various  stages  of 
starvation,  and  in  all  cases  the  susceptibility  has  been  found  to 
increase  during  starvation.  In  P.  velata  also  the  susceptibility  to 
cyanide  has  been  found  to  increase  during  starvation.  This 
species  does  not  undergo  reduction  in  size  as  rapidly  as  P.  doroto- 
cephala, but  the  effect  of  starvation  is  essentially  the  same  in  both. 
If  the  susceptibility  of  these  animals  is  in  any  degree  a  measure  of 


Stages    ■ 

ax 

c\ 

II 

\ 

III 

• 

\\ 
\\ 
\\ 

W 

V 

— 1 1 1— 1 y 

A 
»\ 
\\ 
\\ 

\\ 

\\ 

\\ 
\\ 
\\ 

— 1 — 1 — \ 

lO 


II 


Hours  I  :;  3  4  5  6  7  ^  9 

Fig.  57.— Susceptibility  of  Planaria  dorotocephala  to  KCN  o.ooi  mol.  in  relation 
to  nutritive  condition  and  age:  ah,  dashes,  well-fed,  growing  animals;  ab,  unbroken 
line,  animals  reduced  by  starvation  from  20-24  mm.  to  7-8  mm.;  cd,  animals  from  the 
same  stock  and  of  the  same  size  at  the  beginning  of  the  experiment  as  the  star\'ed 
animals,  but  which  have  been  fed  while  other?  were  starving. 

physiological  age,  the  starving  animals  certainly  undergo  rejuvenes- 
cence, the  degree  of  rejuvenescence  varying  with  the  degree  of 
starvation  and  reduction. 


THE  PRODUCTION  OF  CARBON  DIOXIDE  BY  STARVED  ANIMALS 

The  invention  of  the  Tashiro  biometer  (Tashiro,  '13)  has  made 
possible   a   direct  estimation   and   comparison   of   carbon-dioxide 


NUTRITION  IN  SENESCENCE  AND  REJUVENESCENCE      i6i 

production  in  dilTercnt  individuals  and  pieces  or  tissues  of  small 
animals.  The  agreement  between  the  results  obtained  with  this 
apparatus  and  those  of  the  susceptibility  method  has  already  been 
mentioned  (pp.  73,  74). 

A  number  of  estimations  of  carbon-dioxide  production  in  starved, 
reduced  animals,  as  compared  with  well-fed,  growing  animals  of 
the  same  size,  have  been  made  with  the  aid  of  this  apparatus.' 
The  worms  used  for  the  estimation  of  carbon-dioxide  production 
were  taken  from  a  starvation  stock  after  ninety-four  days  of  star- 
vation. The  animals  were  twenty  to  twenty-four  millimeters 
long  at  the  beginning  of  the  starvation  period,  and  after  ninety- 
four  days  without  food  had  undergone  reduction  to  a  length  of 
seven  millimeters.  In  each  estimation  the  carbon-dioxide  pro- 
duction of  one  of  these  starved  animals  was  compared  with  that 
of  a  young,  well-fed  animal  of  the  same  size. 

Two  estimations  were  made  with  normal  uninjured  animals  and 
in  both  cases  the  carbon-dioxide  production  of  the  starved  animal 
in  a  given  length  of  time  was  slightly  greater  than  that  of  the  fed 
animal.  But  since  the  animals  moved  about  to  some  extent,  and 
since  the  apparatus  is  so  sensitive  that  differences  in  carbon- 
dioxide  production  resulting  from  dift'erences  in  motor  activity 
might  be  a  serious  source  of  error,  it  was  thought  desirable  to  elimi- 
nate movement  as  far  as  possible.  This  was  accomplished  by  re- 
moving the  heads  of  the  two  animals  to  be  compared  and  making 
the  estimation  after  they  had  become  quiet.  These  headless 
animals  remained  quiet  in  the  chambers  of  the  biometer,  but  gave 
essentially  the  same  result  as  those  with  heads.  In  the  two  esti- 
mations made  with  such  animals  the  carbon-dioxide  production  of 
the  starved  animal  was  practically  the  same  as  that  of  the  fed 
animal.  In  other  words,  the  rate  of  production  of  carbon  dioxide 
in  the  starved,  reduced  animal  is  practically  equal  to  that  in  the 
young,  growing  animal  of  the  same  size,  and  this  rate  is  much 
higher  per  unit  of  body  weight  than  that  in  large,  old  animals.  The 
results  obtained  by  the  direct  susceptibiUty  method  are  thus  fully 

'  These  estimates  were  made  at  my  request  by  Dr.  Tashiro  before  the  biometer 
was  available  for  general  use,  and  I  take  this  opportunity  of  aiknowledginK  my  obliga- 
tion to  him,  both  for  conducting  the  experiments  and  for  permitting  me  to  use  the 
results. 


l62 


SENESCENCE  AND  REJUVENESCENCE 


confirmed  by  the  estimations  of  carbon-dioxide  production.  In 
rate  of  carbon-dioxide  production  the  starved,  reduced  animals 
resemble  young  rather  than  old  animals,  such  as  they  were  before 
starvation. 


THE  RATE  OF  DECREASE  IN  SIZE  DURING  STARVATION 

When  the  animals  are  kept  entirely  without  food  the  rate  of 
decrease  in  size  shows  in  general  an  increase,  at  least  during  the 
later  stages  of  starvation.  Thus  far  only  incidental  observations 
have  been  made  concerning  this  point,  the  approximate  lengths  of 
lots  of  animals  being  noted  as  they  were  removed  from  time  to 
time  for  determination  of  the  susceptibility.  But  even  in  these 
measurements  the  differences  in  rate  of  decrease  in  size  appear, 
though  with  some  irregularities,  and  in  most  cases  the  increase  in 
rate  in  the  later  stages  of  starvation  is  evident  without  measure- 
ment. Table  III,  for  which  the  data  are  given  in  Table  II  (p.  157) , 
gives  the  average  length  of  the  animals  in  a  starvation  stock  at 
monthly  intervals,  and  Table  IV  gives  similar  information,  but 

TABLE  III 


Length  of  Starvation 
Period  in  Days 

Length  of  Animals 
in  Millimeters 

Percentage  of 

Decrease  in 

Length 

0 

15     -   18 

10       -    12 

7     -     8 
3-5-     4 

•J2 

30 

60    

QI 

qi 

TABLE  IV 

Length  of  Starvation 
Period  in  Days 

Length  of  Animals 
in  Millimeters 

Percentage  of 

Decrease  in 

Length 

0         

6-7 

4-S 

2-2.5 

22 

?o 

60 

50 

from  a  stock  of  animals  of  smdler  size  before  starvation.  In 
Table  III  the  average  decrease  in  length  during  the  first  month  is 
about  30  per  cent,  during  the  second  about  the  same,  and  during 


NUTRITION  IN  SENESCENCE  AND  REJU\ENESCEXCE     163 

the  third  about  50  per  cent.  Similarly,  in  the  much  smaller  worms 
of  Table  IV  the  average  decrease  in  length  during  the  first  month 
is  30  per  cent,  and  during  the  second,  50  per  cent.  In  these  cases 
the  measurements  for  each  month  were  made  on  different  lots  of 
worms  from  the  same  stock.  Doubtless  a  continuous  series  of 
measurements  of  the  same  individuals  would  bring  out  the  differ- 
ences in  rate  of  decrease  still  more  clearly.  When  the  animals  are 
not  kept  entirely  without  food  the  rate  of  reduction  does  not  in- 
crease, but  may  even  decrease  in  later  stages,  for  the  smaller  the 
animals,  the  more  completely  does  a  small  amount  of  food  retard 
or  inhibit  reduction.  This  increase  in  rate  of  reduction  durinij 
starvation  confirms  the  observations  on  susceptibility  and  on 
carbon-dioxide  production,  for  it  indicates  that  the  rate  of  meta- 
bolic processes  increases  as  reduction  proceeds. 

In  this  connection  the  study  by  Mayer  ('14)  of  loss  of  weight 
in  a  jelly-fish,  Cassiopea,  is  of  interest.     From  his  data  Mayer  con- 
cludes that  the  relative  loss  of  weight  for  each  day  or  other  period 
is  in  general  the  same  throughout  the  course  of  starvation.     More- 
over, the  nitrogen-content  and  water-content  of  the  body  do  not 
show  any  change  in  relation   to  starvation.     At  first  glance  it 
appears  that  the  course  of  starvation  in  this  medusa  differs  from 
that  in  Planaria.     While  the  metabohc  condition  of  the  animals 
during  starvation  has  not  been  determined,  the  constancy  in  the 
percentage  of  loss  of  weight  indicates  that  the  metabohc  rate  does 
not  increase  as  starvation  and  reduction  proceed.     As  a  matter  of 
fact,  however,  Mayer's  data,  and  particularly  the  curves  of  loss 
of  weight,  show  that  in  most  cases  the  loss  of  w-eight  in  uninjured 
animals  during  the  first  two  or  three  weeks  of  starvation  is  slightly 
less  than  the  calculated  loss  according  to  the  formula  which  Mayer 
has  adopted,  while  during  the  later  period  of  starvation  the  obser\-ed 
loss  of  weight  equals  or  in  many  cases  exceeds  the  calculated  loss. 
In  mutilated  animals,  which  arc  undergoing  regeneration  as  well 
as  starvation,  the  observed  loss  of  weight  during  the  earlier  stages 
of  starvation  is  in  most  cases  more  rapid  than  the  calculated  loss, 
but  the  two  coincide  more  nearly  in  later  stages. 

It  is  probable  then  that  Mayer's  law  of  loss  of  weight  is  only  an 
approximation  based  on  averages,  and  that  some  slight  increase 


1 64  SENESCENCE  AND  REJUVENESCENCE 

in  the  percentage  of  loss  in  a  given  time  interval  does  occur  in  unin- 
jured animals.  In  regenerating  animals,  on  the  other  hand,  the 
loss  is  more  rapid  in  earlier  stages  because  of  the  use  of  body  sub- 
stance in  the  formation  of  new  parts  as  well  as  for  function.  As 
regeneration  proceeds,  the  growth  of  the  new  parts  becomes  less 
rapid  and  requires  less  material,  and  the  loss  of  weight  becomes 
sHghtly  less  rapid.  If  these  suggestions  are  correct,  starvation  in 
Cassiopea  follows  essentially  the  same  course  as  in  Planaria  and 
is  accompanied  by  increase  in  metabolic  rate  and  some  degree  of 
rejuvenescence.  For  the  study  of  this  aspect  of  starvation,  how- 
ever, the  medusa  is  a  particularly  unfavorable  form  because  the 
volume  of  cellular  substance  is  exceedingly  small,  as  compared 
with  the  volume  of  gelatinous  material  which,  according  to  Mayer, 
constitutes  the  chief  source  of  nutrition  during  starvation,  and  since 
this  is  extra-cellular,  its  disappearance  does  not  alter  the  cellular 
condition.  For  the  same  reason  changes  in  chemical  constitution 
and  water-content  of  the  protoplasm,  so  far  as  they  occur,  are 
inappreciable,  though  in  an  animal  with  so  little  differentiation  as 
the  medusa  the  changes  are  probably  not  very  great.  There  is 
also  the  possibihty  that,  as  Putter  believes,  substances  in  solution 
in  the  water  serve  as  a  source  of  nutrition  to  some  extent.  If  this 
is  the  case,  the  influence  of  such  substances  on  the  rate  of  loss  of 
weight  must  be  greater  in  the  later  stages  of  starvation  when  the 
animal  is  smaller  and  the  absolute  loss  less  than  in  the  earlier 
stages,  and  will  therefore  contribute  to  mask  the  increasing  rate  of 
loss  in  these  stages.  Taking  all  these  facts  into  account,  it  appears 
highly  probable  that  the  changes  in  the  cellular  substance  of  the 
medusae  are  very  similar  to,  though  probably  less  extensive  than, 
those  in  Planaria.  Mayer  notes  that  the  cells  decrease  in  size, 
their  boundaries  become  indistinct,  and  some  cells  die.  Determina- 
tions of  the  changes  in  susceptibility  of  the  cellular  portions  of  the 
body  of  the  medusa  during  starvation  would  be  of  interest. 

THE  CAPACITY  OF  STARVED  ANIMALS  FOR  ACCLIMATION 

In  general  the  abiHty  of  planarians  to  become  accUmated  to 
depressing  agents  or  conditions  varies  with  the  rate  of  metabolism. 
Young  animals,  for  example,  become  much  more  readily  and  more 


NUTRITION  IN  SENESCENCE  AND  REJU\EXESCE\CE     165 

completely  acclimated  to  cyanide  or  alcohol,  low  temperature, 
etc.,  than  old,  and  accUmation  occurs  more  readily  at  higher  than 
at  lower  temperatures  (Child,  '11).  In  the  low  concentrations  of 
reagents  used  in  the  accUmation  susceptibility  method  (pp.  82-84), 
starved  animals  show  very  Kttle  capacity  for  accHmation  as 
compared  with  well-fed  animals  of  the  same  size;  in  most  cases  even 
less  than  large,  old  animals.  In  my  earher  studies  of  suscepti- 
bihty  only  this  accHmation  method  was  used,  and  since  in  general 
the  capacity  for  accHmation  had  been  found  to  vary  with  the  rate 
of  metabolism,  the  very  sHght  capacity  of  starved  animals  for 
accHmation  was  regarded  as  indicating  that  their  rate  of  metab- 
oHsm  was  low.  But  the  results  obtained  in  later  investigation 
by  the  direct  susceptibiUty  method  which  have  been  briefly  pre- 
sented above,  and  the  confirmation  of  these  by  the  estimations  of 
carbon-dioxide  production,  force  us  to  the  conclusion  that  the 
rate  of  metaboHsm  increases  during  starvation.  This  being  the 
case,  the  decrease  in  capacity  for  accHmation  in  starved  animals 
cannot  be  due  to  a  low  rate  of  metaboHsm,  but  must  be  associated 
with  the  nutritive  condition  in  some  way  independent  of  meta- 
boHc  rate  (Child,  '14).  When  feeding  is  begun  after  a  long  period 
of  starvation,  the  capacity  for  acclimation  rises  almost  at  once 
(Child,  '11)  and  continues  to  increase  as  feeding  continues  and 
growth  replaces  reduction. 

Since  the  nature  of  the  process  of  accHmation  is  at  present 
unknown,  this  relation  between  nutritive  condition  and  capacity 
for  accHmation  cannot  at  present  be  analyzed,  but  must  simply 
be  recorded  as  a  fact.  But  whether  accHmation  results  primarily 
from  a  change  in  the  metaboHc  substratum,  or  in  the  character 
and  relation  of  the  metabolic  reactions,  the  fact  that  the  individual 
with  a  supply  of  nutritive  material  from  external  sources  has  a 
greater  capacity  for  accHmation  than  the  starving  animal  which 
is  undergoing  reduction  is  at  least  suggestive,  as  indicating  the 
greater  possibiHty  of  change  under  changed  external  conditions 
in  the  well-fed  animal. 

Whatever  may  be  the  nature  of  the  relation  between  nutrition 
and  capacity  for  acclimation,  the  facts  demonstrate  that,  although 
the  starved,  reduced  animals  are  practically  identical  with  >oung, 


1 66  SENESCENCE  AND  REJUVENESCENCE 

growing  animals  of  the  same  size  as  regards  rate  of  metabolism, 
they  differ  widely  from  these  in  their  capacity  for  acclimation.  This 
difference  raises  the  question  whether  capacity  for  acclimation  is 
a  fundamental  or  only  an  incidental  feature  of  the  age  cycle.  If 
it  is  a  fundamental  feature,  then  the  reduced  animals  have  under- 
gone rejuvenescence  only  in  certain  respects  and  have  actually 
become  older  physiologically  in  certain  other  respects.  If,  on  the 
other  hand,  it  is  merely  incidental,  then  the  reduced  animals  have 
undergone  what  is  essentially  rejuvenescence  and  merely  require 
food  in  order  to  make  them  identical  with  young,  growing  individuals. 
The  latter  alternative  seems  to  be  the  correct  one.  If  the  decrease 
in  capacity  for  acclimation  during  starvation  is  regarded  as  a 
process  of  senescence,  it  becomes  necessary  to  admit  that  an  animal 
which  is  old  in  this  respect  may  become  young  within  a  few  hours 
when  it  is  fed.  The  susceptibihty  as  measured  by  the  direct  method 
and  the  rate  of  carbon-dioxide  production  are  certainly  much  more 
adequate  criteria  of  physiological  age  and  condition  than  the 
capacity  for  acchmation.  In  other  words,  reduction  by  starva- 
tion is  essentially  a  process  of  rejuvenescence  in  these  animals, 
and  the  difference  between  them  and  young,  growing  animals  as 
regards  capacity  for  acclimation  is  an  incidental  rather  than  a 
fundamental  difference. 

When  the  animal  reduced  by  starvation  is  again  fed,  its  physio- 
logical condition  very  soon  becomes  indistinguishable  from  that  of 
growing  animals  of  about  the  same  size.  In  the  advanced  stages 
of  reduction  the  susceptibility  of  the  reduced  animal  is  almost  always 
somewhat  greater  than  that  of  fed  animals  of  the  same  size,  and  the 
effect  of  renewed  feeding  is  a  decrease  in  susceptibihty  to  about 
the  same  level  as  that  of  the  fed  animal.  The  capacity  for  acch- 
mation, as  already  noted,  increases  even  after  a  single  feeding, 
but  in  advanced  stages  of  reduction  by  starvation  several  feedings 
are  usually  necessary,  i.e.,  the  animal  must  attain  a  well-fed  con- 
dition before  the  capacity  for  acchmation  is  equal  to  that  of  grow- 
ing animals.  The  effect  of  a  single  feeding  may  appear  within  an 
hour  or  two,  but  lasts  at  most  only  a  few  days,  the  animal  rapidly 
returning  to  the  completely  starved  condition.  But  if  other  feed- 
ings follow  at  sufficiently  short  intervals,  growth  soon  begins,  and 


NUTRITION  IN  SENESCENCE  AND  REJUVENESCENCE      167 

both  susceptibility  and  capacity  for  acclimation  undergo  a  gradual 
decrease  as  the  animal  once  more  becomes  physiologically  older. 
After  at  most  a  few  feedings,  then,  the  reduced  animal  is  indistin- 
guishable from  the  young  animal  in  nature,  and,  as  regards  sus- 
ceptibility, carbon-dioxide  production,  and  capacity  for  acclimation, 
is  capable  of  undergoing  senescence  again.  That  a  real  rejuvenes- 
cence has  occurred  during  starvation  cannot  be  doubted. 

PARTIAL  STARVATION  IN  RELATION  TO  SENESCENCE 

The  asexual  life  history  of  Planaria  velata  was  described  in 
chap,  vi  and  it  was  pointed  out  that  in  this  species  the  decrease  in 
rate  of  metabolism  characteristic  of  the  period  of  growth,  differen- 
tiation, and  senescence  apparently  leads  automatically  to  fragmen- 
tation of  the  body  and  so  to  the  reconstitution  from  the  fragments  of 
small,  physiologically  young  animals,  which  repeat  the  hfe  history. 

If  this  process  of  fragmentation  is  associated  with  senescence 
and  if  starvation  and  reduction  bring  about  rejuvenescence,  it 
should  be  possible,  not  only  to  prevent  the  occurrence  of  fragmen- 
tation, but  to  keep  the  animals  indefinitely  at  a  certain  age  by 
giving  them  a  quantity  of  food  just  sufficient  to  prevent  reduction 
but  not  sufficient  to  permit  growth.  This  experiment  has  been 
performed  with  a  stock  of  these  animals.  During  almost  three 
years  they  have  been  fed  at  intervals  varying  from  two  or  three 
days  to  two  or  three  weeks,  the  feeding  being  regulated  according 
to  the  condition  of  the  animals.  If  growth  occurred,  the  intervals 
between  feedings  were  increased,  and  if  the  animals  decreased  in 
size  they  were  fed  with  greater  frequency.  If  some  animals  showed 
more  growth  or  reduction  than  others,  they  were  isolated  and  the 
feedings  regulated  as  required  until  all  were  again  of  approximately 
the  same  size.  During  the  early  stages  of  the  experiment  growth 
was  twice  allowed  to  proceed  too  far,  and  a  few  of  the  larger  worms 
of  the  stock  underwent  some  fragmentation. 

During  the  three  years  of  the  experiment  the  animals  have  been 
kept  at  lengths  varying  from  four  to  seven  millimeters.  In  all 
this  time  no  fragmentation  has  occurred  except  in  the  two  cases 
mentioned  above,  when  growth  was  allowed  to  go  too  far.  The 
animals  are  still  in  good  condition  and  show  the  activity  of  yi)ung 


1 68  SENESCENCE  AND  REJUVENESCENCE 

animals.  Susceptibility  determinations  have  not  been  made,  since 
the  stock  is  not  large  and  is  gradually  depleted  by  occasional  acci- 
dental losses  in  changing  water.  However,  there  is  every  reason  to 
believe  that  the  animals  are  as  young  physiologically  as  their  size 
would  lead  one  to  suspect,  and  they  have  shown  no  indications  of 
the  changes  in  color,  cessation  of  feeding,  and  decrease  in  motor 
activity  characteristic  of  old  worms. 

While  the  animals  of  this  insufficiently  fed  stock  have  remained 
at  essentially  the  same  physiological  age  during  almost  three  years, 
another  portion  of  the  same  original  stock  which  emerged  from 
cysts  in  the  laboratory  at  the  same  time,  but  which  has  been  fed 
often  enough  to  permit  rapid  growth,  has  passed  through  thirteen 
asexual  generations.  A  comparison  of  these  two  stocks  leaves  no 
doubt  as  to  the  effect  of  partial  starvation  in  inhibiting  senescence 
and  the  changes  accompanying  it.  In  these  animals  the  length 
of  life  or  of  the  developmental  period  is  not  measured  by  time,  but 
by  rapidity  of  growth.  With  abundant  food  this  species  may  pass 
through  its  whole  life  history,  from  the  stage  of  emergence  from  a 
cyst  to  fragmentation  and  encystment,  in  three  or  four  weeks,  but 
when  growth  is  prevented  by  loss  of  food,  it  may  continue  active 
and  young  for  at  least  three  years,  as  the  foregoing  experiment  has 
demonstrated,  and  doubtless  for  a  much  longer  period.  It  is  of 
course  possible  that  continuation  of  the  experiment  during  a  suffi- 
ciently long  time  might  show  that  a  slow  process  of  senescence  was 
occurring  in  spite  of  the  absence  of  growth.  Only  such  continua- 
tion can  determine  whether  this  will  be  the  case  or  not.  But  the 
fact  remains  that  senescence  can  be  retarded  or  inhibited  for  a 
length  of  time,  which,  compared  with  the  length  of  the  active  hfe 
in  nature,  is  very  long — in  the  present  case  about  thirty-six  times 
as  long,  and  eighteen  times  as  long  as  the  average  length  of  a  genera- 
tion in  the  laboratory. 

Similar  experiments  with  Planaria  dorotocephala  have  been 
carried  sufficiently  far  to  show  that  this  species  also  can  be  kept 
in  approximately  the  same  physiological  condition  for  some  months. 
As  long  as  the  animals  do  not  receive  food  enough  to  permit  growth, 
there  are  no  indications  of  senescence,  but  when  growth  occurs  the 
susceptibihty  begins  to  decrease. 


NUTRITION  IN  SENESCENCE  AND  REJU\'ENESCEXCE      169 

In  these  experiments  with  partial  feeding  the  susceptibiUtv 
does  not  of  course  remain  the  same  at  all  times.  Each  feeding  is 
followed  by  a  distinct  decrease  in  susceptibility,  and  later,  as  the 
animals  begin  to  starve,  the  susceptibility  increases  again.  Thus 
the  life  of  such  animals  actually  consists  of  alternating  periods  of 
senescence  and  rejuvenescence.  But  if  the  intervals  between 
feedings  are  sufficient,  the  changes  in  the  two  opposite  directions 
balance  each  other  and  the  mean  physiological  condition  remains 
the  same. 

THE    CHARACTER    OF    NUTRITION    IN   RELATION    TO    THE    AGE    CYCLE 

Up  to  the  present  time  the  problem  of  the  relation  between  the 
character  of  nutrition  and  the  Hfe  cycle  has  received  comparatively 
little  attention,  although  it  is  evident  from  the  results  already 
obtained  that  an  interesting  and  important  field  of  investigation 
is  open  here.  In  the  attempt  to  find  a  suitable  food  for  the  breeding 
of  Planaria  velata  in  the  laboratory  it  was  soon  observed  that  the 
size  attained  before  the  animals  ceased  to  feed,  the  character  of 
fragmentation,  and  even  its  occurrence  and  the  physiological  con- 
dition of  the  small  animals  which  develop  from  the  encysted  frag- 
ments, were  all  dependent  to  some  extent  upon  the  character  of 
nutrition.  In  these  experiments  the  food  did  not  in  all  cases  con- 
sist of  single  tissues  or  organs,  so  that  it  is  not  possible  to  correlate 
the  effects  produced  with  the  characteristics  of  particular  tissues 
and  still  less  with  particular  chemical  constitution.  There  is  no 
doubt,  however,  that  this  species  constitutes  favorable  material 
for  nutrition  experiments  of  this  kind,  such,  for  example,  as  Gudcr- 
natsch  ('12,  '14)  and  Romeis  ('13,  '14)  have  carried  out  on  the  tad- 
pole, using  various  tissues  and  organs,  including  thyroid,  thymus, 
adrenals,  etc.,  as  nutritive  material. 

Only  certain  important  points  in  the  feeding  exixTiments  on 
F.  velata  need  be  mentioned  here.  When  the  animals  are  fed  beef 
liver  the  Hfe  cycle  approaches  more  closely  to  that  oi  animals  in 
nature  than  with  any  other  food  thus  far  used,  but  cessation  of 
feeding  and  fragmentation  occur  at  a  smaller  size  than  in  nature. 
The  liver-fed  animals  also  differ  from  animals  in  nature  in  not 
losing  their  pigment  before  fragmentation  and  in  encysting  rather 


lyo  SENESCENCE  AND  REJUVENESCENCE 

frequently  without  fragmentation.  The  encysted  fragments  from 
liver-fed  animals  give  rise  to  physiologically  young  animals  which 
are  able  to  repeat  the  life  cycle,  and  asexual  breeding  may  be  con- 
tinued with  liver  as  food  through  at  least  many  generations. 

Animals  fed  with  earthworm  have  a  rather  different  life  history. 
They  attain  a  larger  size  before  fragmentation  and,  when  kept  at  a 
low  temperature,  they  continue  to  grow  until  very  much  larger 
than  any  individuals  ever  seen  in  nature,  and  finally  die,  apparently 
of  old  age,  usually  without  fragmentation  and  always  without 
sexual  reproduction.  At  higher  temperatures  they  cease  to  feed 
at  a  certain  stage,  and  some  give  rise  to  two  or  a  few  fragments 
which  are  usually  larger  than  under  natural  conditions.  Some 
animals  encyst  whole  without  fragmentation,  and  some  do  not 
encyst  at  all. 

The  further  history  of  these  different  groups  is  of  interest.  The 
encysted  fragments  give  rise  to  physiologically  young  worms.  The 
animals  which  encyst  without  fragmentation  remain  in  the  cysts 
until  they  have  used  up  their  reserves  and  more  or  less  of  their  own 
tissues,  and  then  emerge  as  smaller,  physiologically  younger  animals 
also  capable  of  repeating  the  hfe  cycle.  But  the  history  of  the 
animals  which  do  not  encyst  shows  the  most  interesting  features. 
The  normal  form  of  a  full-grown,  well-fed  animal  is  shown  in  Fig  8 
(p.  94).  At  the  time  these  animals  cease  to  feed,  the  pharynx 
disintegrates  and  no  new  pharynx  develops  in  its  place.  In  the 
course  of  a  few  days  the  posterior  end  of  the  body  becomes  inactive 
and  assumes  a  rounded  form,  as  in  Fig.  58,  being  dragged  about 
by  the  rest  of  the  body  as  if  it  were  a  dead  mass  or  a  foreign  sub- 
stance. During  the  next  few  days  this  change  in  form  and  behav- 
ior extends  farther  anteriorly,  so  that  the  rounded  mass  becomes 
larger  and  the  active  portion  of  the  body  smaller  (Fig.  59).  At 
this  stage  this  process  may  cease  in  some  individuals,  but  in  others 
it  continues  still  farther,  as  in  Fig.  60,  until  only  a  short  anterior 
portion  with  the  head  remains  active.  In  this  condition  the  small, 
active  anterior  region  is  scarcely  able  to  drag  the  large  inert  mass 
about,  although  it  makes  violent  attempts  to  do  so. 

In  some  cases  the  rounded  mass  disintegrates  at  this  stage  and 
is  lost,  and  the  anterior  region  slowly  undergoes  reconstitution  to  a 


NUTRITION  IN  SENESCENCE  AND  REJUVENESCENCE      171 

whole  animal  of  small  size  by  development  of  a  new  posterior  end 
and  a  pharynx  (Fig.  65),  and  is  once  more  ready  to  feed  and  repeat 


Figs.  58-65.— P/awar/a  velala:    a  life  cycle  without  reproduction:    KIrs.  58-61, 
the  changes  of  advanced  age;  Figs.  62-65,  the  period  of  rejuvenescence. 

the  life  history.     But  in  other  cases  the  change  in  form  continues 
until  nothing  but  the  head  remains  active,  as  in  Fig.  Oi.  and  then 


172  SENESCENCE  AND  REJUVENESCENCE 

disintegration  begins  and  the  whole  animal,  including  the  head, 
dies.  In  the  rounded  mass  the  internal  structure  gradually  dis- 
appears with  extensive  necrosis  and  disintegration  of  cells,  until 
little  more  than  a  sack  remains  containing  some  living  tissue  and  a 
large  amount  of  granular  substance  resulting  from  the  cell  disinte- 
gration. In  other  words,  this  mass  represents  to  a  large  extent  a 
process  of  involution  and  death  of  cells  and  tissue. 

In  those  individuals  in  which  this  process  of  involution  ceases 
at  the  stage  of  Fig.  59  or  Fig.  60,  the  mass  usually  does  not  undergo 
complete  disintegration,  but  remains  attached  to  the  body  and  is 
gradually  resorbed,  the  process  extending  over  a  month  or  two. 
During  this  time  the  mass  evidently  serves  as  a  source  of  nutrition 
for  the  active  region  and  is  in  some  sense  analogous  to  the  yolk 
sac  of  many  embryos.  In  such  individuals  the  anterior  region 
remains  continuously  active  and  the  involution  mass  gradually 
becomes  smaller  (Figs.  62  and  63),  until  completely  resorbed  and 
only  a  longer  or  shorter  anterior  region  considerably  reduced  in 
size  remains.  In  cases  where  the  resorption  of  the  posterior  mass 
begins  at  a  stage  like  that  of  Fig.  59,  the  portion  of  the  body  remain- 
ing after  complete  resorption  may  include  the  anterior  half,  but 
where  resorption  does  not  begin  until  involution  is  more  advanced, 
as  in  Fig.  60,  the  portion  remaining  after  resorption  may  be  only 
the  anterior  fourth  (Fig.  64). 

After  resorption  of  the  posterior  mass  is  completed,  the  remain- 
ing portion  slowly  undergoes  reconstitution,  developing  a  new 
posterior  end  and  a  new  pharynx  and  mouth  (Fig.  65),  and  thus 
finally  attaining  the  same  condition  as  in  those  cases  where  the 
involution  mass  disintegrates  and  is  lost  without  resorption.  At 
this  stage  the  small  animal  is  physiologically  young,  as  its  high 
susceptibihty  indicates,  and  is  again  ready  to  take  food  and  grow 
and  repeat  the  life  cycle. 

In  this  remarkable  process  of  senescence  and  death  of  a  part  of 
the  body  and  rejuvenescence  of  the  remainder,  no  reproductive 
process  is  involved  except  the  reconstitution  of  the  anterior  region 
into  a  new  whole.  That  portion  of  the  body  which  under  natural 
conditions  undergoes  fragmentation  and  encystment,  the  fragments 
undergoing  reconstitution  to  new  animals,  is  in  these  cases  appar- 


NUTRITION  IN  SENESCENCE  AND  REJUVENESCENCE      1 73 

ently  too  far  advanced  in  senescence  to  recover,  and  undergoes 
complete  death  and  disintegration  or  gradual  degeneration  and 
resorption.  That  it  serves  as  a  source  of  nutrition  for  the  portion 
which  remains  active  is  indicated  by  the  fact  that  the  reduction 
in  size  of  this  portion  is  much  less  rapid  than  in  starving  normal 
animals.  Nevertheless,  it  is  evident  that  the  supply  of  food 
in  the  involution  mass  is  not  adequate  to  prevent  the  occurrence  of 
reduction  sooner  or  later,  and  since  the  animal  during  resorption 
of  the  posterior  region  is  without  pharynx  or  mouth,  it  cannot  take 
food  in  the  usual  way;  consequently  as  the  source  of  supply  in  the 
involution  mass  gradually  fails,  the  anterior  region  graduallv 
starves  and  undergoes  reduction.  But  when  a  certain  stage  of 
reduction  is  reached,  the  new  posterior  end  and  phar}'nx  develop 
at  the  expense  of  other  regions,  and  the  process  of  rejuvenescence 
is  completed.  In  these  cases,  then,  senescence  leads  to  death  in 
certain  parts  of  the  body  while  other  parts  remain  alive  and  undergo 
rejuvenescence  by  starvation,  reduction,  and  reconstitution. 

The  question  of  the  conditions  concerned  in  the  localization  of 
death  in  the  posterior  region  of  the  body  requires  some  considera- 
tion. The  facts  indicate  that  fragmentation  is  usually  inhibited 
by  certain  internal  conditions  and  that,  as  the  rate  of  metabolism 
decreases  during  senescence,  the  lower  limit  for  the  continued 
existence  of  differentiated  structure  is  finally  reached  and  passed 
in  the  posterior  region,  and  the  processes  of  involution  or  disinte- 
gration begin.  The  earthworm  diet  has  been  repeatedly  used  with 
animals  of  different  stocks  and  the  results  are  always  essentially 
the  same.  Continued  feeding  in  successive  generations  of  the  same 
stock  has  not  thus  far  brought  about  any  further  changes,  and  the 
animals  which  do  not  die  show  no  indications  of  progressive  senes- 
cence in  successive  generations. 

Another  diet  used  consists  of  the  bodies  of  fresh-water  mussels. 
The  portions  used  for  food  are  chiefly  the  reproductive  organs  and 
the  digestive  gland,  and  the  animals  apparently  eat  chietly  the 
reproductive  cells. 

In  the  first  generation  the  effect  of  this  diet  is  to  decrease  the 
frequency  of  fragmentation.  In  most  animals  the  involution  of 
the  posterior  region  occurs,  as  in  Figs.  58-61.  but  ver>-  commonly 


174  SENESCENCE  AND  REJUVENESCENCE 

this  process  ends  with  the  death  of  the  whole  animal  and  no  resorp- 
tion or  rejuvenescence  occurs.  In  some  animals,  however,  the 
involution  mass  disintegrates  and  is  lost  at  the  stage  of  Fig.  60, 
and  the  anterior  portion  develops  a  new  pharynx  and  posterior  end. 
With  the  mussel  diet  a  few  very  small  fragments  arise  from  some 
individuals. 

The  animals  which  undergo  partial  involution  and  disintegration 
followed  by  reconstitution  feed  a  few  times  on  mussel,  but  cease 
to  grow  at  about  half  the  size  of  the  preceding  generation,  and  most 
of  them  undergo  involution  and  die.  Some  encyst  entire  and  others 
produce  one  or  two  fragments  and  then  encyst,  but  in  all  cases  thus 
far  the  encysted  animals  or  pieces  die  in  the  cysts  and  no  third 
generation  appears,  i.e.,  that  portion  of  the  second  generation  which 
arises  from  the  non-encysting  members  of  the  first  generation  dies 
without  giving  rise  to  a  third  generation. 

As  regards  the  encysted  fragments  from  the  first  generation, 
about  half  die  in  the  cysts,  the  others  emerge  as  small  worms; 
these  feed  a  few  times  on  mussel,  grow  slowly  to  about  half  the  size 
of  the  first  generation,  and  undergo  involution  or  in  a  few  cases 
fragmentation,  as  in  the  preceding  generation.  Most  of  these 
worms  die  at  this  time,  either  as  the  result  of  involution  or  in  the 
cysts,  but  a  very  few  emerge  from  cysts  as  a  third  generation. 
These  scarcely  react  to  food  at  all,  show  almost  no  growth,  and  soon 
undergo  involution  and  die  with  or  without  fragmentation,  or 
die  in  the  cysts.  In  no  case  has  a  single  animal  of  the  fourth  gener- 
ation been  obtained  from  stocks  fed  on  mussel,  and  very  few  live 
to  the  third  generation. 

These  stocks  show  every  indication  of  a  progressive  senescence 
in  successive  generations.  It  is  of  interest  to  note  that  a  few  of  the 
animals  from  encysted  fragments  reach  the  third  generation,  while 
the  animals  developed  from  the  pieces  surviving  partial  involution 
or  encystment  without  fragmentation  all  die  in  the  second  genera- 
tion. The  encysted  fragments  are  smaller  than  the  others  and 
undergo  more  extensive  reorganization,  and  consequently  a  some- 
what greater  degree  of  rejuvenescence  in  the  process  of  reconstitu- 
tion to  whole  animals.  But  the  animals  after  emergence  from  cysts 
or  reconstitution  following  partial  involution  are  not  as  young 


NUTRITION  IX  SENESCENCE  AND  REJUVEXESCENCE      175 

physiologically  as  those  kept  on  other  diets.  Their  susceptibility 
is  distinctly  lower  than  that  of  animals  at  the  same  stage  in  nature 
or  in  stocks  kept  on  a  diet  of  liver  or  earthworm.  Their  motor 
activity  is  also  less  than  that  of  these  animals  and  their  rate  of 
growth  is  slow.  There  can  be  no  doubt  that  these  animals  undergo 
much  less  rejuvenescence  in  the  reproductive  and  reconstitutional 
processes  than  do  those  on  the  other  diets,  and  it  is  evident  that  the 
degree  of  rejuvenescence  is  progressively  less  in  each  successive 
generation. 

These  experiments  with  different  diets  have  been  described  at 
some  length  because  they  demonstrate  that  the  course  of  the  life 
cycle  may  be  very  greatly  altered  by  the  character  of  nutrition. 
The  effect  of  the  mussel  diet  is  to  a  certain  degree  inherited  and 
cumulative  from  one  generation  to  another  and  in  this  respect 
differs  from  that  of  the  other  diets.  The  chief  value  of  these 
experiments  lies  in  their  suggestiveness  as  indicating  what 
may  be  accomplished  with  diets  carefully  limited  to  particular 
kinds  of  cells  or  tissues  or  to  substances  of  particular  chemical 
constitution. 

REFERENCES 

CmLD,  C.  M. 

1911.  "A  Study  of  Senescence  and  Rejuvenescence  Based  on  E.xperiments 
with  Planarians,"  Arcli.f.  Entwickelungsmech.,  XXXI. 

1914.  "Starvation,  Rejuvenescence  and  Acclimation  in  Planaria  doro- 
tocepliala,"  Arch.f.  Entwickelungsmech.,  XXXX'III. 

Citron,  E. 

1902.  "Beitrage  zur  Kenntnis  von  Syncorync  sarsii,"  Arch.  f.  Xalurgc- 
schichte,  Jhg.  LXVIII. 

DOWNEROWITSCH. 

1892.  "On  the  Changes  in  the  Spinal  Cord  during  Complete  Starvation" 
(Russian),  Bolnitschnaja  Gasela  Bolkina,  1892. 

GUDERNATSCH,  J.  F. 

191 2.  "Feeding  Experiments  on  Tadpoles:  I,  The  Influence  of  Specific 
Organs  Given  as  Food  on  Growth  and  Differentiation,"  Arch. 
f.  Entwickelungsmech.,  XXX\'. 

1914.  "Feeding  Experiments  on  Tadpoles:  II,  .\  Further  Contribution 
to  the  Knowledge  of  Organs  of  Internal  Secretion,"  Am.  Jour,  of 
Anal.,  X\'. 


176  SENESCENCE  AND  REJUVENESCENCE 

Heumann,  G. 

1850.  Mikroskopische  Untersuchimgen  an  hungernden  und  verhungerten 
Tauben.  Giessen.  (Referat  aus  Canstatt's  J ahresberichte  il.  d. 
Fortschritte  d.  gcs.  Med.,  I,  1851.) 

Kasanzeff,  W. 

1901.  Experimcntelle  Untersuchimgen  iiher  "Paramecium  caudatum." 
Dissertation.     Zurich. 

LiLLIE,  F.  R. 

1900.  "Some  Notes  on  Regeneration  and  Regulation  in  Planarians," 
Am.  Nat.,  XXXIV. 

LUKJANOW,    S. 

1897.     "L 'Inanition  du  noyau  cellulaire,"  Rev.  Scient.,  1897. 

Mayer,  A.  G. 

1914.  "The  Law  Governing  the  Loss  of  Weight  in  Starving  Cassiopea," 
extract  from  Carnegie  Instil.  Puhl.  i8j. 

MORGULIS,  S. 

191 1.  "Studies  of  Inanition  in  Its  Bearing  upon  the  Problem  of  Growth," 
Arch.  f.  Entwickelungsmech.,  XXXII. 

^lORPURGO,  B. 

1888.  "SuU  processo  fisiologico  di  neoformazione  cellulare  durante  la 
inanizione  acuta  dell'  organismo,"  Arch.  Sci.  Med.,  XII. 

1889.  "  Sur  la  Nature  des  atrophies  par  inanition  chez  les  animaux  a  sang 
chaud,"  Arch.  Ital.  de  Biol.,  XII. 

RiNDFLEISCH. 

1868.     Lehrhuch  der  pathologischen  Gewebe.    Bd.  III. 

ROMEIS,  B. 

1913.  "Der  Einfluss  verschiedenartiger  Ernahrung  auf  die  Regeneration 
bei  Kaulquappen  (Rana  esculenta),"  I,  Arch.  f.  Entwickelungs- 
mech., XXXVII. 

1914.  "Experimcntelle  Untersuchungen  iiber  die  Wirkung  innersekreto- 
rischer  Organe:  II,  Der  Einfuss  von  Thyreoidea-  und  Thymusfut- 
terung  auf  das  Wachstum,  die  Entwicklung  und  die  Regeneration," 
Arch.  f.  Entwickelungsmech.,  XL,  XLI. 

SCHULTZ,  E. 

1904.  "tJber  Reduktionen:  I,  Uber  Hungererscheinungen  bei  Planaria 
lactea,"  Arch.  f.  Entwickelungsmech. ,  XVIII. 

Statkewitsch,  p. 

1894.  "ijber  Veranderungen  des  Muskel-  und  Driisengewebes,  sowie 
des  Herzganglien  beim  Hungern,"  Arch.  J.  e.xp.  Pathol,  u.  Pharm., 
XXXIII. 


NUTRITION  IN  SENESCENCE  AND  REJUVENESCENCE      177 

Stoppenbrink,  F. 

1905.     "Der  Einfluss  herabegesetzter  Emahrung  auf  den  hislologischcn 
Bau  der  Siisswassertricladen,"  Zcitschr.J.  wiss.  Zool..  LXXIX. 
Tashiro,  S. 

1913.  "A  New  Method  and  Apparatus  for  the  Estimation  of  Exceedingly 
Minute  Quantities  of  Carbon  Dioxide,"  Am.  Jour,  of  Physiol  , 
XXXII. 

Wallengren,  H. 

1902.  "Inanitionscrscheinungcn  der  Zelle.  Untersuchungen  an  Proto- 
zoen,"  Zeitschr.f.  allgem.  Physiol.,  I. 


CHAPTER  VIII 

SENESCENCE  AND  REJUVENESCENCE  IN  THE  LIGHT  OF  THE 

PRECEDING  EXPERIMENTS 

REVIEW  AND  ANALYSIS  OF  THE  EXPERIMENTAL  DATA 

In  addition  to  the  differences  in  size,  structure,  and  behavior 
which  constitute  more  or  less  definite  criteria  of  age  in  the  lower 
organisms,  characteristic  differences  in  rate  of  metabolism  have 
been  shown  to  exist,  the  rate  being  highest  in  the  youngest  animals 
and  decreasing  with  advancing  age.  These  age  differences  in  rate 
of  metabolism  are  sufficiently  well  marked,  as  compared  with  such 
individual  and  incidental  differences  as  occur  under  ordinary  con- 
ditions, to  make  possible  their  use  as  criteria  of  physiological  age, 
and  so  to  compare  the  physiological  ages  of  different  individuals. 

In  this  way  it  has  been  shown  that,  in  general,  physiological 
senescence  accompanies  the  productive  and  progressive  processes, 
i.e.,  growth,  specialization,  morphogenesis,  and  differentiation,  and 
that  physiological  rejuvenescence  is  a  feature  of  reduction  and  of 
processes  associated  with  the  reconstitution  and  agamic  develop- 
ment in  nature  of  new  individuals  from  parts  of  a  pre-existing 
individual. 

There  can,  I  think,  be  httle  question  that  among  the  experiments 
described  the  reduction  experiments  are  most  significant.  Here 
the  possible  compHcations  connected  with  reproduction  and  recon- 
stitution are  absent,  and  only  loss  of  substance  with  the  changes 
conditioned  by  it  occurs.  The  association,  on  the  one  hand,  of 
physiological  rejuvenescence  with  reduction,  and,  on  the  other, 
of  senescence  with  growth  and  differentiation,  not  only  demon- 
strates that  rejuvenescence  is  not  necessarily  associated  with 
reproduction,  but  also  constitutes  a  positive  experimental  foun- 
dation for  a  physiological  conception  of  the  age  changes.  It  is 
evident  that  in  the  organism  in  which  differentiation  has  begun 
and  is  progressing  the  addition  of  substance  brings  about  in  some 
way  a  decrease  in  metabohc  rate  and  so  a  decrease  in  the  capacity 
for  further  growth  and  development,  while  the  removal  of  substance 

178 


CONCLUSIONS  FROM  EXPERIMENTS  179 

by  starvation  increases  the  rate  of  metabolism  and  so  the  capacity 
for  growth  and  development.  From  an  advanced  physiological 
age  it  is  possible  to  bring  the  animals  back  practically  to  the  begin- 
ning of  post-embryonic  life  by  forcing  them  to  use  up  and  eliminate 
the  substance  which  they  have  accumulated  during  post-embr\-onic 
growth  and  development.  Here  no  reproductive  process,  asexual 
or  sexual,  is  involved,  but,  to  return  to  the  analog>'  between  the 
organism  and  the  flowing  stream,  the  metabolic  current  is  forced 
to  erode  its  channel  instead  of  depositing  material  along  its  course. 

These  experiments  leave  no  basis  for  the  contention  that  the 
organism  or  the  cell  cannot  become  young  after  it  has  once 
undergone  senescence,  and  that  the  only  source  of  youth  is  an 
undifferentiated  germ  plasm.  The  planarian  reduced  by  starva- 
tion consists  entirely  or  almost  entirely  of  cells  which  formed 
functional  differentiated  parts  of  the  original,  physiologically  and 
morphologically  old  animal,  but  after  renewed  feeding  it  is  younger 
in  every  respect  and  in  all  parts  of  the  body,  so  far  as  can  be  deter- 
mined, than  before  starvation,  and  is  again  capable  of  growth  and 
senescence.  In  short,  these  experiments  demonstrate  that  the 
differentiated  somatic  cells  can  return  to  a  physiological  condition 
which  at  least  approaches  that  of  embryonic  or  unditlerentiated 
cells,  and  there  is  no  reason  for  believing  that  a  hypothetical 
parcel  of  germ  plasm  in  the  nucleus  of  these  cells  is  in  any  way 
responsible  for  this  regression.  The  results  of  these  physiological 
experiments  are  in  complete  agreement  with  the  conclusions  reached 
by  E.  Schultz  ('04,  '08),  on  the  basis  of  morphological  data. 

The  few  experiments  on  the  influence  of  the  kind  of  nutrition 
upon  the  course  of  the  life  cycle  indicate  clearly  that  the  course  and 
results  of  senescence  may  differ  widely  with  the  character  of  the 
food.  The  experiments  do  not  throw  any  light  on  the  question  of 
the  factors  concerned  in  the  differences  produced,  but  with  more 
complete  control  of  the  kind  of  nutrition  more  definite  results  on 
this  point  will  doubtless  be  possible.  Even  these  e.xperiments 
show,  however,  that  the  age  cycle  in  these  lower  animals  is  by  no 
means  independent  of  nutritional  factors.  Perhaps  the  most 
important  point  is  that  with  certain  foods  a  progressive  senescence 
from   generation    to   generation   occurs,    while   with    other    ioods 


i8o  SENESCENCE  AND  REJUVENESCENCE 

senescence  and  rejuvenescence  apparently  balance  each  other  in 
each  cycle.  Evidently  certain  physiological  characteristics  of  the 
organism,  which  are  associated  either  with  its  metabolic  processes 
or  with  its  structural  substratum,  or  more  probably  with  both, 
are  dependent  upon  the  character  of  its  nutrition,  to  such  an  extent 
at  least  as  to  modify  the  age  cycle  very  essentially. 

In  the  hght  of  the  starvation  experiments  the  occurrence  of 
rejuvenescence  in  connection  with  the  reconstitution  of  pieces  and 
with  agamic  reproduction  in  nature  is  not  difhcult  to  understand. 
In  the  reconstitution  of  pieces  some  cells  undergo  dedifferentiation 
to  a  greater  or  less  extent  and  take  part  in  the  development  of  new 
structures,  or  the  new  parts  arise  from  cells  which  have  remained 
relatively  young  and  less  specialized  than  others;  some  cells  may 
undergo  degeneration  and  disappear  completely,  and,  except  where 
the  isolated  piece  takes  food,  the  energy  for  the  various  changes  is 
derived  from  reserves  and  from  the  tissues  themselves  which 
undergo  more  or  less  reduction. 

The  degeneration  of  differentiated  cells  does  not  contribute 
directly  to  the  rejuvenescence  of  the  piece,  but  if  cells  undergo 
dedifferentiation  or  if  the  new  structures  arise  from  cells  which 
have  retained  a  more  or  less  "embr^^onic"  condition,  the  result  is 
of  course  a  younger  organism.  And  if  in  addition  any  appreciable 
amount  of  reduction  occurs,  rejuvenescence,  particularly  in  the 
old  parts  which  constitute  the  chief  source  of  nutritive  supply  in 
such  cases,  proceeds  still  farther. 

We  have  seen  that  the  degree  of  rejuvenescence  varies  with  the 
size  of  the  piece  and  with  the  degree  of  reconstitution,  i.e.,  the 
degree  of  approach  to  wholeness  in  the  piece.  The  reason  for  these 
relations  is  clear.  Provided  reconstitution  occurs,  the  smaller 
the  piece  the  greater  the  loss  of  old  structure  and  the  devel- 
opment of  new,  and  the  greater  the  reduction  of  the  whole  piece 
in  furnishing  energy  for  the  process.  Moreover,  the  greater  the 
degree  of  reconstitution,  the  greater  the  reorganization,  and  the 
greater  the  supply  of  nutritive  material  required  from  the  piece. 

Thus  in  the  piece  undergoing  reconstitution  a  new  metabolic 
equilibrium  is  attained.  The  parts  formed  anew  are  young  and 
have  a  higher  rate  of  metabohsm  than  the  others,  but  they  become 


CONCLUSIONS  FROM  EXPERIMENTS  i8l 

older  and  their  rate  decreases  as  they  grow  and  difTerentiatc.  At 
the  same  time,  the  remaining  parts  of  the  piece  are  drawn  upon 
as  a  source  of  energy  for  the  growth  of  the  new  parts,  and  in  con- 
sequence they  undergo  reduction  and  their  rate  of  metabolism 
rises:  in  fact,  they  become  younger.  Sooner  or  later  a  condition  is 
attained  in  which  the  young,  new  parts  can  no  longer  grow  at  the 
expense  of  the  old  parts  because  the  rate  of  metabolism  in  the  former 
is  decHning  while  that  in  the  latter  is  increasing.  When  this  stage 
is  attained  reconstitutional  changes  can  proceed  no  farther.  If 
the  animal  is  fed  at  this  stage  it  grows  essentially  like  any  other 
animal,  and  if  not  fed  it  undergoes  reduction  like  any  other  stars-ed 
animal.  At  the  time  equilibrium  is  attained  the  rate  of  metabolism 
in  general  will  vary  with  the  size  of  the  piece  and  the  degree  of 
reconstitution.  The  smaller  the  piece  and  the  greater  the  amount 
of  reconstitutional  change,  the  higher  the  rate  at  which  this  equi- 
librium is  reached,  and  so  the  younger  the  animal  becomes  during 
reconstitution. 

As  already  noted,  the  cases  of  agamic  reproduction  examined 
in  chap,  vi  do  not  differ  fundamentally  from  the  experimental 
reproductions  or  reconstitutions  following  the  physical  isolation 
of  pieces,  and  we  should  expect  that  if  rejuvenescence  occurs  in 
the  one  case  it  would  in  the  other.  Whether  a  piece  develops  into 
a  new  whole  as  the  result  of  artificial  isolation  by  section  or  other 
means,  or  of  physiological  isolation  by  conditions  arising  in  the 
organism  in  nature,  the  result  is  essentially  the  same.  In  one 
respect,  however,  there  is  a  difference  of  degree:  in  many  cases  of 
budding,  fission,  etc.,  the  new  developing  individual  remains  in 
organic  continuity  with  the  parent  until  its  development  is  ad- 
vanced or  completed  and  so  is  supplied  with  nutritive  material. 
In  such  cases,  as  for  example,  in  hydra,  the  new  individual,  instead 
of  undergoing  reduction,  grows  throughout  its  development,  and 
the  degree  of  rejuvenescence  is  much  less  marked  than  in  those 
cases  where  the  tissues  of  the  developing  piece  or  region  are  the 
source  of  energy.  Here  the  deditTerentiation  of  cells,  or  the  su!)- 
stitution  of  less  dilTerentiated  younger  cells  for  those  previously 
existing,  are  the  chief  factors  in  rejuvenescence,  although  appar- 
ently some  degree  of  metabolic  equilibration  does  occur  in  the  old 


1 82  SENESCENCE  AND  REJUVENESCENCE 

parts,  i.e.,  these  parts  become  somewhat  younger,  even  though 
nutrition  is  present. 

The  results  of  the  experiments  together  with  the  results  of 
observation  in  nature  constitute  an  adequate  foundation  for  the 
conclusion  that  a  greater  or  less  degree  of  rejuvenescence  must  be 
associated  with  agamic  reproduction.  As  we  have  seen  in  the  case 
of  Pennaria  (pp.  148-51),  it  may  be  less  in  the  more  specialized 
than  in  the  less  specialized  types  of  reproduction  and  it  must 
differ  in  degree  with  various  other  conditions,  but  wherever  recon- 
stitutional  or  reductional  changes  are  involved  we  must  expect 
to  find  some  degree  of  rejuvenescence. 

The  persistence  of  the  embryonic  condition  in  the  growing  tip 
and  meristematic  tissues  of  the  higher  plants  and  in  the  growing 
regions  of  many  of  the  lower  animals  shows,  however,  that  under 
certain  conditions  growth  may  continue  over  long  periods  of  time 
without  any  very  great  degree  of,  and  in  many  cases  perhaps 
without  any,  senescence.  So  far  as  we  know,  the  long-continued 
persistence  of  the  embryonic  condition  in  rapidly  growing  tissues 
is  always  associated  with  a  high  frequency  of  cell  or  nuclear  division, 
and  the  experiments  on  the  infusoria  (see  pp.  137-42)  indicate 
that  at  least  in  these  forms  some  degree  of  rejuvenescence  occurs 
in  connection  with  cell  division.  There  is  every  reason  to  beheve 
that  in  nuclear  and  cell  division  in  general,  as  in  other  forms  of 
reproduction,  some  degree  of  change  in  the  direction  of  rejuvenes- 
cence occurs.  Whether  this  balances  the  changes  which  occur 
between  successive  cell  divisions  depends  upon  the  frequency  of 
division,  the  rate  of  growth,  and  various  other  conditions.  Where 
a  balance  is  attained  or  approached,  differentiation  and  senescence 
do  not  occur,  or  proceed  slowly;  otherwise  they  proceed  more  or 
less  rapidly,  according  to  conditions. 

The  only  possible  conclusion  in  view  of  all  the  facts  seems  to  be 
that  senescence  is  associated  with  the  productive  and  progressive 
phases,  and  rejuvenescence  with  the  reductive  and  regressive 
phases,  of  the  life  cycle. 

THE  NATURE  OF  SENESCENCE  AND  REJUVENESCENCE 

The  theories  of  senescence  that  have  been  advanced  fall  mainly 
into  two  groups.     Those  of  the  one  group  regard  the  phenomena 


CONCLUSIONS  FRO^I  EXPERLMENTS  183 

of  senescence  as  in  some  sense  secondary  or  incidental,  and  not  as 
a  necessary  and  inevitable  consequence  or  a  part  of  the  cycle  of 
development.  According  to  such  theories  senescence  is  due  to 
incomplete  excretion  of  toxic  products  of  metabolism  of  one  kind 
or  another,  or  to  a  wearing  out  of  certain  organs  for  one  reason  or 
another,  to  evolutionary  adaptation,  or  to  some  other  incidental 
factor.  The  theories  of  the  other  group  regard  senescence  as  a 
result  of  the  same  processes  which  determine  growth,  differentia- 
tion, and  what  we  call  development  in  general.  These  theories 
attempt  to  find  the  conditions  and  processes  which  determine 
senescence  in  the  conditions  and  processes  which  underlie  develop- 
ment. From  this  point  of  view  senescence  is  a  feature  of  develop- 
ment. The  experimental  data  presented  in  the  preceding  chapters 
leave  little  room  for  doubt  that  both  senescence  and  rejuvenescence 
are  necessary  and  inevitable  features  of  the  life  cycle.  Certainly 
the  worn-out  organs  of  old  animals  cannot  be  repaired  by  an 
extended  period  of  starvation,  nor  is  the  eHmination  of  toxic  meta- 
boHc  products  likely  to  be  assisted  by  the  structural  degeneration 
of  parts  which  occurs  in  various  cases  of  reconstitution.  Senescence 
and  development  are  simply  two  aspects  of  the  same  complex 
dynamic  activities. 

Since  our  knowledge  of  the  metabolic  reactions,  on  the  one  hand, 
and  of  the  colloid  substratum  of  the  organism,  on  the  other,  is  not 
very  far  advanced,  we  cannot  at  present  determine  the  exact  nature 
of  the  relation  between  growth,  differentiation,  and  senescence,  and 
reduction,  dedifferentiation,  and  rejuvenescence.  Nevertheless  we 
can  point  with  considerable  confidence  to  certain  features  of  growth 
and  development  as  afi'ording  a  basis  for  the  changes  of  the  age 
cycle. 

It  was  pointed  out  in  Part  I  that  during  development  the 
general  metabolic  substratum  of  the  organism,  the  unspecialized 
or  embryonic  cell,  undergoes  a  progressive  change  in  the  direction 
of  greater  physiological  stability  in  consequence  of  changes  in  the 
substratum  and  additions  to  it  in  the  course  of  growth  and  differ- 
entiation. The  general  result  of  these  changes  is  a  decrca.se  in  the 
metaboHc  activity  of  each  unit  of  weight  or  volume  of  the  organism 
because  the  proportion  of  the  relatively  stable  constituents  in  the 
substratum  increases. 


1 84  SENESCENCE  AND  REJUVENESCENCE 

Such  changes  are  most  conspicuous  in  those  cells  which  become 
loaded  with  non-protoplasmic  inclosures,  such  as  granules  or 
droplets,  or  in  which  the  cytoplasm  is  largely  transformed  into  the 
inactive  substance  of  skeletal  or  supporting  tissues,  but  it  is  evident 
that  similar  changes  occur  to  a  greater  or  less  extent  in  all  cells 
during  differentiation.  Development  must  then  be  accompanied 
by  a  progressive  decrease  in  the  rate  of  metabolism  per  unit  of 
weight  or  volume  of  the  substance  of  the  organism. 

But  other  factors  are  probably  more  or  less  generally  concerned 
in  bringing  about  the  decrease  in  metabolic  rate  which  occurs 
during  development.  It  is  a  familiar  fact  that  emulsoid  colloid 
sols  and  gels  outside  the  organism  undergo  changes  in  aggregate 
condition  with  time.  The  degree  of  aggregation  increases,  the 
water-content  decreases,  and  shrinkage  occurs.  To  what  extent 
such  changes  occur  in  the  colloids  of  the  living  organism  is  a  ques- 
tion, but  that  there  is  more  or  less  change  of  this  sort  in  the  more 
stable  portions  of  the  colloid  substratum  is  highly  probable,  and  in 
any  case  the  continued  accumulation  of  colloids  in  the  cell  as  a 
product  of  metabolism  probably  brings  about  an  increase  in  con- 
centration and  of  aggregation  in  the  colloid.  The  rate  of  chemical 
reaction  in  a  colloid  substratum  is  more  or  less  intimately  associated 
with  the  condition  of  the  colloid  and  very  generally  decreases  with 
increasing  aggregation.  The  increasing  density  and  aggregation  of 
the  colloid  substratum  may  lead,  then,  to  an  actual  decrease  in  the 
rate  of  chemical  reactions.  Moreover,  the  increase  in  density  and 
thickness  and  the  decrease  in  the  permeability  of  membranes  may 
retard  the  exchange  through  them.  The  retardation  of  enzyme 
activity  by  accumulation  of  the  products  may  also  play  a  part  in 
decreasing  metabolic  rate,  though  it  is  probable  that  such  decreases 
in  metabohc  activity  are  usually  less  permanent  than  the  age 
changes  and  are  associated  with  other  shorter  periods  in  the  Hfe 
of  the  organism.  Various  other  factors,  as  yet  unrecognized, 
may  also  be  concerned,  but  it  is  evident  in  any  case  that  the  decrease 
in  rate  of  metabohsm  is  a  part  of  development  itself  and  not  an 
accidental  or  incidental  feature  of  life.  The  decrease  in  metaboUc 
rate  during  development  is  in  fact  a  necessary  and  inevitable 
consequence  of  the  association  of  the  chemical  reactions  which 


CONCLUSIONS  FROM  EXPERIMENTS  i8c 

constitute  metabolism  with  a  colloid  substratum  i)r()(lu(C'(l  by  thr 
reactions. 

The  development  of  metabolic  mechanisms,  such  as  the  striated 
muscles,  which  are  capable  when  stimulated  of  a  ver>'  hi^'h  rate  of 
metabohsm,  is  in  no  sense  an  exception  to  or  a  contradiction  of  the 
general  law  that  a  decrease  in  rate  of  metabolism  is  associated  with 
development.  In  the  early  stages  of  development  correlative 
functional  stimulation  of  the  cells  of  the  organism  certainly  occurs 
only  to  a  very  slight  degree,  so  far  as  it  occurs  at  all,  and  cannot  bt- 
compared  to  the  degree  of  functional  stimulation  which  occurs 
in  later  stages  after  development  of  the  stimulating  mechanism — 
in  the  case  of  striated  muscle,  the  nervous  system.  This  being  the 
case,  we  must  compare  the  rate  of  metabolism  in  the  unstimulated 
or  very  slightly  stimulated  differentiated  cell — not  the  rate  of  the 
cell  under  strong  stimulation — with  the  rate  of  the  embr^'onic  cell, 
if  we  are  to  attain  a  correct  conception  of  the  difiference.  Bearing 
this  point  in  mind,  it  is  easy  to  see  how  great  the  ditTerence  in 
rate  is.  In  the  case  of  striated  muscle,  for  example,  the  rate  of 
metabolism  in  the  earher  stages  of  development  is  sufficiently 
high  to  bring  about  the  morphogenesis  of  the  muscle  without  the 
accelerating  influence  of  nerve  impulses,  but  later  the  muscle 
atrophies  unless  its  rate  is  frequently  accelerated  bv  nervous 
stimulation. 

From  this  point  of  view  senescence  in  its  dynamic  aspect  con- 
sists in  a  decrease  in  the  rate  of  metabolism  determined  by  the 
changes  in  the  substratum  during  development,  and,  in  its  morpho- 
logical aspect,  in  the  changes  themselves.  The  idea  that  senescence 
is  in  one  way  or  another  simply  an  aspect  or  result  of  development 
itself  has  been  more  or  less  clearly  expressed  by  various  authors, 
and  various  features  of  the  developmental  process  have  been  re- 
garded as  the  essential  factors,'  but  discussion  of  the  different 
theories  is  postponed  to  a  later  chapter. 

Attention  has  already  been  called  to  the  fact  that  growth  may 
give  place  to  reduction  and  progressive  development  to  regressive. 

'  Among  more  recent  writers  who  have  advanced  this  view  in  one  form  or  another 
arc  the  following:  Cholodkowsky,  '8^;  Enriqucs,  '07,  'og;  Jickcli,  "oj;  Ka,sM.>wiu, 
'99;  Minot,  '08,  '13,  and  several  papers  of  earlier  date;  Muhlmann,  '00,  '10. 


1 86  SENESCE^XE  AND  REJUVENESCENCE 

In  reduction,  substance  previously  accumulated  in  the  cell  is 
broken  down  as  a  source  of  energy  and  eliminated  or  serves  for  new 
syntheses,  and  the  cell  undergoes  regression  toward  the  embryonic 
condition.  Such  a  change  means  the  removal  to  a  greater  or  less 
extent  of  the  conditions  which  have  brought  about  a  decrease  in 
rate  of  metabolism,  the  proportion  of  less  stable  to  more  stable 
substance  increases,  the  aggregation  of  the  substratum  decreases, 
and  the  rate  of  metabolism  increases.  These  changes  constitute 
rejuvenescence.  Dynamically  rejuvenescence  consists  in  increase 
in  rate  of  metabohsm  and  morphologically  in  the  changes  in  the 
substratum  which  permit  increase  in  rate. 

If  this  definition  of  rejuvenescence  is  correct,  it  follows  that 
there  is  no  necessary  relation  between  rejuvenescence  and  gametic 
or  any  other  kind  of  reproduction.  The  changes  in  the  substratum 
may  result  from  reduction  connected  with  starvation,  or  from  some 
change  in  the  character  of  metabolism  which  brings  about  the 
removal  of  certain  substances  previously  accumulated,  as  well  as 
from  the  reductional  and  reconstitutional  changes  connected  with 
the  reproduction  of  cells,  parts  of  a  complex  organism,  or  new 
whole  organisms.  And  earlier  chapters  have  demonstrated  that 
not  only  agamic  reproduction  in  nature  and  experimental  reproduc- 
tion, but  also  reduction  by  starvation  may  bring  about  rejuvenes- 
cence to  such  an  extent  that  the  animals  thus  produced  are  as 
young  physiologically  as  sexually  produced  animals  in  the  same 
morphological  stage.  And,  finally,  as  will  appear  in  chaps,  xiii-xv, 
the  facts  indicate  that  in  the  cycle  of  gametic  reproduction  the 
period  of  gamete  formation  is  a  period  of  senescence  and  that  of 
early  embryonic  development  a  period  of  rejuvenescence. 

As  regards  the  conception  of  the  nature  of  senescence,  this 
theory  does  not  dift'er  fundamentally  from  others  which  have  been 
advanced  at  various  times,  but  in  its  emphasis  upon  the  occurrence 
and  significance  of  rejuvenescence  it  departs  from  commonly 
accepted  views.  The  idea  that  life  proceeds  only  in  one  direction 
from  youth  to  age  and  death  must  be  abandoned.  Rejuvenescence 
is  as  essential  a  feature  of  life  as  senescence.  Senescence  often 
leads  inevitably  and  automatically  through  reproduction  or  reduc- 
tion and  dedift'erentiation  to  rejuvenescence. 


CONCLUSIONS  FRO^r  EXPERIMENTS  187 

PERIODICITY  IN  ORGANISMS  IN  RELATION  T(J  THE  AGE  CYCLE 

Before  leaving  the  question  of  the  nature  of  senescence  and 
rejuvenescence  it  is  necessary  to  call  attention  to  their  relation  to 
other  periodic  or  cyclical  changes  in  the  organisms.  According 
to  the  conception  developed  here,  there  is  nothing  unique  in  the 
processes  of  senescence  and  rejuvenescence;  they  are,  on  the  con- 
trary, of  the  same  general  character  as  many  other  changes  in  rate 
of  metaboUsm  in  the  organism,  the  chief  difference  being  that  the 
factors  concerned  in  the  age  changes  are  the  more  stable  and  less 
rapidly  changing  features  of  the  substratum,  while  other  shorter 
cycles  may  result  from  changes  in  less  stable  features.  In  fact, 
it  is  not  possible  to  make  any  sharp  distinction  between  the  age 
changes  and  many  other  periodicities.  The  differences  are  differ- 
ences of  degree  rather  than  of  kind.  Recognition  of  this  fact  is 
important,  because  senescence  has  often  been  regarded  as  a  rather 
mysterious  process,  quite  different  from  anything  else  in  the  life 
cycle,  but  the  experimental  evidence  points  to  a  very  different 
conclusion. 

The  more  or  less  regularly  periodic  or  cyclical  changes  are  among 
the  most  conspicuous  and  characteristic  features  of  living  organisms. 
They  range  in  the  individual  from  momentary,  evanescent  changes, 
such  as  occur  in  stimulation  and  the  return  to  the  original  condition 
which  follows,  to  the  changes  of  the  age  cycle  which  often  coincide 
with  the  whole  Hfe  of  the  individual.  Some  of  these  periodic  changes 
are  of  course  directly  determined  by  external  conditions,  such  as 
temperature,  light,  etc.,  while,  as  regards  others,  internal  factors 
are  more  important.  Any  extended  consideration  of  these  various 
periodicities  is  quite  beyond  the  present  purpose,  but  the  fact  that 
many  of  them  seem  to  be  more  or  less  similar  in  character  to  the 
age  cycle,  except  as  regards  the  time  factor,  demands  some  sort  of 
interpretation.  According  to  the  physico-chemical  conception  of 
the  organism,  many  different  periodic  changes  in  rate  of  metabolism 
are  possible,  for  different  conditions  in  the  substratum  which  accel- 
erate or  retard  the  rate  of  metabolism  may  arise  and  disappear  with 
very  different  rapidity,  and  the  variety  of  more  or  less  dehnitely 
periodic  phenomena  in  life  is  in  full  agreement  wilii  theoretical 
possibility. 


1 88  SENESCENCE  AND  REJUVENESCENCE 

A  simple  case  in  point  is  the  accumulation  of  carbon  dioxide 
which  decreases  the  rate  of  metaboHsm  in  a  very  short  time,  while 
recovery  occurs  as  rapidly  when  it  is  ehminated.  According  to 
the  theory  of  stimulation  by  R.  S.  Lillie  ('09a,  '096),  the  concen- 
tration of  carbon  dioxide  in  the  cell  is  the  chief  factor  in  decreasing 
the  rate  of  reaction  after  stimulation.  LiUie  suggests  that  in  the 
absence  of  excitation  the  plasma  membrane  of  cells  is  impermeable 
or  only  slightly  permeable  to  carbon  dioxide,  consequently  the  car- 
bon dioxide  resulting  from  metabolism  accumulates  in  the  cell 
and  decreases  the  rate  of  metabohsm.  A  stimulus  is  any  external 
factor  which  increases  the  permeability  of  the  membrane  to  carbon 
dioxide  and  so  permits  its  escape  from  the  cell  and  consequently 
brings  about  an  increase  in  rate  of  metabolism,  which  is  followed  by 
a  decrease  in  rate  as  the  temporary  increase  in  permeability  of  the 
membrane  disappears. 

Fatigue,  i.e.,  the  decrease  in  rate  of  metabolism  which  follows 
continued  stimulation,  is  generally  believed  to  be  due  to  the  accu- 
mulation of  toxic  products  of  metabohsm  (see  p.  297).  During  rest 
these  products  are  ehminated  and  recovery  occurs.  Various  meta- 
bohc  intoxications  are  probably  very  similar  in  character,  although 
in  many  of  these  cases  the  toxic  substances  are  the  products  of  metab- 
ohsm of  micro-organisms  and  not  of  the  affected  organism  itself. 
The  decreased  metabohc  activity  which  occurs  after  feeding  in 
many  animals  is  undoubtedly  due  to  accumulation  of  some  sub- 
stance or  substances  which  decrease  the  rate  of  reaction.  As  the 
accumulated  substance  disappears,  activity  increases  until  feeding 
again  takes  place. 

In  these  and  many  other  cases  the  changes  in  metabolism  are 
readily  and  rapidly  reversible,  because  the  substances  or  conditions 
which  determine  them  are  readily  ehminated  or  are  themselves 
reversible.  Moreover,  except  where  the  activity  of  the  cell  is 
largely  accumulatory  or  secretory,  these  changes  are  not  ordinarily 
accompanied  by  any  very  marked  morphological  changes.  When 
extreme  or  long  continued,  however,  stimulation  may  bring  about 
very  considerable  structural  changes,  even  in  cells  where  functional 
activity  is  largely  dynamic  rather  than  structural,  such,  for  example, 
as  the  nerve  cells,  in  which  the  morphology  of  function  has  been 


CONCLUSIONS  FROM  FA'PERIMENTS  189 

described  by  various  authors.'  As  might  he  expected,  such 
changes,  if  they  do  not  proceed  beyond  a  certain  Hmit,  are  reversible, 
and  recovery  occurs  rapidly. 

In  cells  where  function  is  accompanied  by  extensive  accumula- 
tion and  discharge  of  substances,  such,  for  example,  as  the  gland 
cells,  storage  cells,  etc..  the  cycles  of  activity  and  morphological 
change  are  essentially  age  cycles,  that  is  to  say.  the  period  of  loading 
of  the  cell  is  a  period  of  decreasing  metabolic  activity,  of  "senes- 
cence," and  the  period  of  discharge  one  of  increasing  activity,  of 
"rejuvenescence,"  which  makes  possible  a  repetition  of  the  cycle. 
In  such  cells  the  structural  changes  are  often  ver>'  marked.  In  the 
pancreas,  for  example,  the  cell  which  is  loaded  with  the  granules 
which  give  rise  to  the  secretion  presents  a  ver}'  different  appearance 
from  the  cell  after  continued  stimulation  and  discharge. 

Figs.  66-68  show  dift'erent  stages  in  the  cyclical  changes  of  the 
pancreas  cells  of  the  toad.  Fig.  66  shows  the  loaded  cells  ready  to 
secrete  when  stimulated.  The  whole  outer  portion  of  the  cell, 
i.e.,  the  part  next  to  the  duct,  is  filled  with  large  granules,  and 
cytoplasm  appears  only  near  the  base  about  the  nucleus.  This 
condition  is  analogous  to  that  of  advanced  differentiation  in  which 
the  cytoplasm  has  been  largely  transformed  into  substances  which 
are  inactive  or  less  active.  In  this  loaded  condition  the  pancreas 
cell  is  only  very  slightly  active  metaboUcally,  and  its  activity  is 
probably  due  in  large  measure  to  the  fact  that  it  does  secrete 
slightly,  and  so  the  substance  of  the  granules  is  being  changed  and 
ehminated  to  some  extent,  more  or  less  continuously. 

But  when  stimulated  to  secretion,  the  ox\'gen  consumption  of 
the  cell  increases  greatly  (Barcroft,  oS).  the  granules  rapidly 
disappear,  and  the  cytoplasmic  zone  extends  from  the  base  of  the 
cells  out  toward  the  periphery.  Fig.  67  shows  four  cells  in  various 
stages  of  discharge  and  Fig.  68,  cells  after  long-continued  stimula- 
tion. In  this  condition  the  cell  is  again  capable  of  a  high  rate  of 
metaboHc  activity;  if  nutrition  is  present  the  process  of  loading 
occurs  once  more,  and  the  cell  approaches  quiescence. 

'See,  for  example.  Dolley,  '13,  '14;  Hodge,  '92,  '94;  Lu^'aro,  '95;  .Mann.  95; 
Pick,  '98;  Pugnat,  '01;  \alenza,  '96.  Further  references  concerning  iK-riodic  and 
other  functional  changes  in  structure  will  be  found  in  these  papers. 


1 9© 


SENESCENCE  AND  REJUVENESCENCE 


This  cycle  of  changes,  which  may  occur  within  a  few  hours  and 
which  may  be  repeated  in  a  single  cell,  is,  I  believe,  not  funda- 
mentally different  from  the  age  cycle  in  organisms.  All  the  essen- 
tial features  of  both  senescence  and  rejuvenescence  up  to  a  certain 


Figs.  66,  67. — Pancreas  cells  of  toad:  Fig.  66,  fully  loaded  and  almost  quiescent; 
Fig.  67,  partially  discharged  after  stimulation.  From  preparations  loaned  by  R.  R. 
Bensley. 

point  are  present.  The  cell  probably  does  not  return  to  the  em- 
bryonic condition  at  any  point  in  the  cycle,  but  it  certainly  does 
undergo  changes  similar  in  character  to  those  of  the  age  cycle, 
though  their  period  is  short.  At  the  same  time  the  gland  cell 
may  be  undergoing  senescence  in  the  stricter  sense,  that  is,  more 


CONCLUSIONS  FROM  EXPERIMENTS 


191 


stable  components  of  the  protoplasm  may  be  accumulatinj,'  or 
undergoing  changes  which  are  not,  or  not  wholly,  compensated 
by  the  functional  cycle. 

Other  gland  cells  undergo  very  similar  periodic  changes  in 
structure,  the  whole  peripheral  region  being  discharged  bodily  in 
some  cases  and  the  cell  regenerating  from  a  small  basal  portion. 
Many  other  cells  in  the  organism  not  regarded  as  gland  cells  pa.ss 
through  somewhat  similar  cycles.  Various  cells,  for  example, 
accumulate  reserves,  such  as  starch  in  plants  and  fat  in  animals 
and  various  other  substances.     As  the  loading  of  such  cells  pro- 


FiG.  68. — Pancreas  cells  of  toad  almost  completely  discharged  after  prolonged 
stimulation.     From  preparations  loaned  by  R.  R.  Bensley. 

ceeds,  they  approach  quiescence,  but  when  conditions  change  so 
that  the  previously  accumulated  substances  are  removed,  they  may 
undergo  a  rejuvenescence.  Although  we  have  at  present  little 
positive  knowledge  along  this  line,  it  seems  probable  that  various 
periodic  changes  in  organisms  or  parts  are  of  this  general  character. 
Quiescent  periods  following  periods  of  abundant  nutrition  and 
accumulation  of  substance  occur  in  the  protozoa  and  other  lower 
animals  as  well  as  in  many  plants,  particularly  in  parts  sjiecialized 
as  storage  organs,  such  as  bulbs,  tubers,  etc.  It  is  a  familiar  tact 
that  in  certain  tropical  species  of  trees  the  loss  of  leaves,  followed 
by  a  quiescent  period,  occurs  at  dilTerent  times  on  different  branches 


192  SENESCENCE  AND  REJUVENESCENCE 

of  the  same  tree.'  In  such  cases  the  periodicity  may  perhaps  be 
associated  with  the  alternate  accumulation  and  removal  of  sub- 
stance. It  is  also  possible  that  periods  which  appear  superficially 
to  be  seasonal  may  be  at  least  often  of  this  character.  Schimper 
believed  that  an  internally  determined  periodicity  might  occur 
independently  of  climatic  and  other  conditions.  Klebs,  however, 
denies  the  existence  of  such  periodicity,  yet  at  the  same  time  he 
regards  the  accumulation  of  organic  substances,  which  as  products 
of  enzyme  activity  inhibit  or  retard  further  activity,  as  a  factor  in 
bringing  about  quiescent  periods.  If  such  substances  are  produced 
more  rapidly  than  they  are  used,  they  must  accumulate,  and  it  seems 
probable  that,  at  least  sometimes,  an  internally  determined  perio- 
dicity may  result. 

The  view  that  the  formation  of  the  gametes  or  sex  cells  is  essen- 
tially a  process  of  differentiation  and  senescence  and  the  early 
stages  of  embryonic  development  a  process  of  rejuvenescence  has 
already  been  mentioned  and  will  be  discussed  more  fully  in  later 
chapters.  The  cycle  of  changes  in  the  egg  is  somewhat  similar  to 
that  in  the  gland  cell,  with  the  difference  that  in  the  egg  the  yolk 
becomes  a  source  of  energy  and  substance  for  growth. 

If  the  point  of  view  advanced  here  is  correct,  then  the  age  cycle 
in  the  strictest  sense  is  merely  one  of  many  periodicities  or  cycles 
in  organisms,  some  longer,  some  shorter,  which  result  from  the  rela- 
tions existing  between  the  chemical  reactions  of  metabolism  and 
the  substratum  in  which  they  occur.  The  distmction  between  an 
age  cycle  and  other  cycles  is  but  Httle  more  than  a  matter  of  con- 
venience or  custom.  The  changes  which  fall  into  the  category  of 
what  we  are  accustomed  to  call  age  changes  are  merely  those  in 
which  the  more  stable  and  less  rapidly  changing  features  of  the 
organism  are  involved.  Various  other  cycles  of  different  length 
differ  mainly  in  that  less  stable  and  more  rapidly  changing  condi- 
tions in  the  substratum  are  concerned.  Whether  we  call  one  cycle 
an  age  cycle  and  another  something  else  is  of  little  importance,  except 
as  regards  convenience.  From  the  cycle  of  fatigue  and  recovery 
at  one  extreme,  to  the  cycle  of  senescence  and  rejuvenescence 
in   the  stricter  sense  at   the   other,   there   are   many  intermedi- 

•  See,  for  example,  Schimper,  '98,  pp.  260-81;  Klebs,  '11;  Volkens,  '12;  Simon,  '14. 


CONCLUSIONS  FROM  EXPERIMENTS  193 

ate  cycles.  In  some  of  these  the  products  of  metaboHsm  accumulate 
only  temporarily,  and  the  period  may  cover  only  a  few  moments  or 
a  few  hours,  while  in  others  the  fundamental  features  of  organic 
structure  are  concerned,  and  the  period  coincides  with  the  life  cycle. 

SENESCENCE  AND  REJUVENESCENCE  IN  EVOLUTION 

It  is  pertinent,  at  this  time,  at  least  to  raise  the  question  whether 
the  point  of  view  and  the  conclusions  reached  from  the  study  of 
individuals  have  any  value  beyond  the  individual  life  cycle.  1^ 
there  any  indication  of  the  progressive  senescence  of  species  or 
groups,  and,  if  such  senescence  occurs,  does  it  always  lead  to  death, 
i.e.,  extinction,  or  is  rejuvenescence  possible  ?  On  the  other  hand,  is 
continued  existence  of  a  species  without  senescence  possible  ? 

Any  answers  to  these  questions  must  at  the  present  time  be  Uttle 
more  than  guesses.  It  is  possible,  however,  that  the  metabolic 
substratum  of  the  species  may  undergo  very  gradual  progressive 
changes  of  the  same  general  character  as  those  concerned  in  indi- 
vidual senescence,  but  which  are  not  entirely  eliminated  or  com- 
pensated during  the  periods  of  individual  rejuvenescence,  and  it  is 
conceivable  that  under  altered  conditions  regression  might  occur  as 
in  individual  rejuvenescence.  It  is  also  possible  that  the  union  of 
two  gametes  from  different  lines  of  descent  in  gametic  reproduction 
may  be  an  important  factor  in  retarding  or  accelerating  such 
changes,  if  they  occur. 

The  records  of  paleontology  are  so  fragmentary  antl  our  igno- 
rance of  the  factors  involved  in  the  extinction  or  persistence  of 
species  is  so  great  that  positive  answers  to  these  questions  cannot  be 
looked  for  in  that  direction.  Certainly  many  species  have  become 
extinct  in  the  course  of  geological  time,  but  whether  their  extinction 
has  in  any  case  been  the  result  of  a  senescence  we  cannot  deter- 
mine. Decreasing  numbers  or  decreasing  size  preceding  extinction 
may  be  due  entirely  to  external  conditions.  But  certain  forms,  such 
for  example  as  Limulus,  the  horseshoe  crab,  and  the  brachiopcxl 
Lingula,  have  persisted  practically  unchanged  from  exceedingly 
remote  geological  periods.  Have  such  species  not  undergone  senes- 
cence, or  has  a  rejuvenescence  occurred  somewhere,  or  perhaps 
periodically,  in  the  course  of  their  descent  ? 


194  SENESCENCE  AND  REJUVENESCENCE 

That  a  process  similar  to  senescence  has  occurred  in  the  evolu- 
tion of  the  higher  organisms  from  the  lower  is  suggested  by  various 
lines  of  evidence.  The  protoplasmic  substratum  of  the  higher  forms 
is  certainly  more  stable  and  undergoes  structural  alteration  less 
readily  and  less  extensively  than  in  the  lower.  The  higher  forms 
undergo  a  greater  degree  of  differentiation  during  development 
than  the  lower,  and  in  the  higher  animals  the  capacity  for  agamic 
and  experimental  reproduction  is  absent  and  growth  is  limited. 
Moreover,  the  metabolic  activity  for  each  unit  of  weight  is  prob- 
ably less  under  similar  conditions  of  temperature,  oxygen  supply, 
nutrition,  etc.,  in  the  higher  than  in  the  lower  forms,  even  in  early 
stages  of  development.  In  short,  there  are  various  resemblances 
between  the  course  of  evolution  and  that  of  individual  development, 
and  the  latter  is  a  period  of  senescence.  And  as  in  the  individual 
altered  conditions  may  bring  about  rejuvenescence,  so  in  the  course 
of  evolution  the  occurrence  of  rejuvenescence  is  conceivable.  If  a 
secular  senescence  of  protoplasm  has  constituted  a  factor  in  evolu- 
tion, the  protoplasm  of  the  higher  forms  must  have  undergone  this 
change  more  rapidly  than  that  of  those  which  remained  as  lower 
forms.  Moreover,  such  a  senescence  might  proceed  more  or  less 
independently  of  the  environment,  though  the  course  and  rate  of 
the  change  would  doubtless  be  influenced  by  environmental  con- 
ditions. In  other  words,  protoplasmic  senescence,  if  it  plays  any 
part  in  evolution,  is  to  some  extent  an  internal  factor,  and  evolution 
itself  is  in  some  degree  a  progressive  change  from  less  to  more 
stable  equilibrium,  rather  than  in  the  opposite  direction. 

The  purpose  of  the  present  section  is  to  suggest  possibiHties, 
rather  than  to  develop  theories.  Since  there  is  continuity  of  pro- 
toplasmic substance  from  generation  to  generation,  there  may  be 
internally  determined  progressive  change  in  that  substance  similar 
in  some  degree  to  the  change  during  individual  life  (see  pp.  464-65). 

REFERENCES 
Barcroft,  J. 

1908.     "Zur  Lehre  vom  Blutgaswechsel  in  den  verschiedenen  Organen," 
Ergebn.  d.  Physiol.,  VII. 

Cholodkowsky,  N. 

1882.     "Tod  und  Unsterblichkeit  in  der  Tierwelt,"  Zool.  Anzeiger,  V. 


CO.XCLUSIONS  FROM  EXIM'RIMKNTS  19- 

CONKLIN,  E.  G. 

1912.  "Cell  Size  and  Nuclear  Size,"  Jour,  of  Exp.  Zool.,  XII. 

1913.  "The  Size  of  Organisms  and  of  Their  Constituent  Parts  in  Rela- 
tion to  Longevity,  Senescence  and  Rejuvenescence,"  Pop.  6V1. 
Monthly,  August,  1913. 

DOLLEY,  D.  H. 

1913.  "The  Morphology  of  Functional  Activity  in  the  Ganglion  Cells 
of  the  Crayfish,  Cambarus  virilis,"  Arch.  f.  Zcllforsch.,  IX. 

1914.  "On  a  Law  of  Species  Identity  of  the  Nucleus-Plasma  Norm  for 
Nerve   Cell    Bodies   of    Corresponding  Ty-pe,"   Jour,   of  Comp 
Neurol.,  XXIV. 

Enriques,  p. 

1907.     "La  morte,"  Riv.  di  Sci.,  Ann.  I. 

1909.  "Wachstum  und  seine  analytische  Darstellung,"  Biol.  Ccnlralbl 
XXIX. 

Hodge,  C.  F, 

1892.  "A  Microscopical  Study  of  Changes  Due  to  Functional  Activity 
in  Nerve  Cells,"  Jour,  of  MorphoL,  VH. 

1894.  "A  Microscopical  Study  of  the  Nerve  Cell  during  Electrical 
Stimulation,"  Jour,  of  MorphoL,  IX. 

JlCKELI,  C.  F. 

1902.    Die  Unvollkommenheit  des  Stofwechsels,  etc.     Berlin. 
Kassowitz,  M. 

1899.     Allgemeine  Biologie.     Wien. 

Klebs,  G. 

191 1.  "Uber  die  Rhythmik  in  der  Entwicklung  der  Pflanzen,"  Sitzungs- 
ber.  d.  Heidelberger  Akad.  d.  Wiss.:  Math,  naturwiss.  Kl. 

LiLLIE,  R.  S. 

1909(7.  "On  the  Connection  between  Changes  of  Permeability  and 
Stimulation  and  on  the  Significance  of  Changes  in  Permeability  to 
Carbon  Dioxide,"  Am.  Jour,  of  Physiol.,  XXIW 

1909^.  "The  General  Biological  Significance  of  Changes  in  the  Permea- 
bility of  the  Surface  Layer  or  Plasma  Membrane  of  Living  Cells." 
Biol.  Bull.,  XVII. 

LUGARO,  E. 

1895.  "Sur  les  modifications  des  cellules  nerveuses  dans  les  divers  etats 
fonctionnels,"  Arch.  Ital.  de  Biol.,  XXIV. 

Mann,  G. 

1895.  "Histological  Change  Induced  in  Sympathetic,  Motor  and  Sensory 
Nerve  Cells  by  Functional  Activity,"  Jour,  of  Attat.  and  Physiol., 
XXIX. 


196  SENESCENCE  AND  REJUVENESCENCE 

MiNOT,  C.  S. 

1908.     The  Problem  of  Age,  Growth  arid  Death.     New  York. 

1913.  Moderne  Probleme  der  Biologie.     Jena. 

MUHLMANN,    M. 

1900.  Uber  die  Ursache  des  Alters.     Wiesbaden. 

1910.     "Das  Altera  und  der  physiologische  Tod,"  Sammlung  anat.  u. 
physiol.  Vortr.,  H.  XL 

Pick,  F. 

1898.  "tjber  morphologische  Differenzen  zwischen  ruhenden  und 
erregten  Ganglienzellen,"  Deutsche  med.  Wochenschr.,  XXII. 

PUGNAT,  C.  A. 

1901.  "Modifications  histologiques  des  cellules  nerveuses  dans  la  fa- 
tigue," Jour,  de  Physiol,  et  de  Pathol,  gen.,  III. 

SCHIMPER,  A.  F.  W. 

1898.     Pjlanzen-Geo graphic  auf  physiologischer  Grundlage.     Jena. 

SCHULTZ,  E. 

1904.     "tJber  Reduktionen:   I,  Uber  Hungererscheinungen  bei  Planaria 

lactea,"  Arch.  f.  Ehtwickelungsmech.,  XVIII. 
1908.     "Uber   umkehrbare  Entwickelungsprozesse  und  ihre  Bedeutung 

fiir  eine  Theorie  der  Vererbung,"  Vortr.  und  Aufs.  it.  Entwicke- 

lungsmech.,  IV. 

Simon,  S.  V. 

1914.  "Studien  uber  die  Periodicitat  der  Lebensprozesse  der  in  dauemd 
feuchten  Tropengebieten  heimischen  Baume,"  Jahrbilcher  J.  wiss. 
Bot.,  LIV. 

Valenza,  G.  B. 

1896.  "I  cambiamenti  microscopici  della  cellula  nervosa  nell'  attivita 
funzionale  e  sotto  I'azione  di  agenti  stimolanti  e  distruttori," 
Atti  R.  Acad.  Scienze  fisiche  e  nat.  di  Napoli,  VII. 

VOLKENS,  G. 

191 2.    Laubfall  und  Lauberneuerung  in  den  Tropen.     Berlin. 


PART  III 

INDIVIDUATION  AND   REPRODUCTION  IN   RELATION  TO  THE 

AGE  CYCLE 


CHAPTER  IX 

INDIVIDUATION  AND  REPRODUCTION  IX  ORGANISMS 

THE  PROBLEM 

Living  organisms  exist  as  more  or  less  definite  individuals.  An 
individual  may  be  provisionally  defined  as  a  more  or  less  complex 
entity  which  acts  to  some  extent  as  a  unit  or  whole.  Such  a  defi- 
nition emphasizes  the  unity  of  the  individual,  but  atTords  no  clue 
to  the  integrating  factor  or  factors,  i.e.,  to  that  which  makes  a 
unity,  a  whole  out  of  the  complex. 

Two  very  conspicuous  characteristics  of  the  organic  individual, 
particularly  in  its  more  highly  developed  forms,  are  its  orderly 
behavior  and  the  definiteness  of  form  and  structure  which  is  one 
feature  of  this  behavior.  Nowhere  do  these  characteristics  appear 
more  clearly  than  in  the  remarkable  sequence  of  events  which  con- 
stitutes what  we  call  the  development,  the  ontogeny  of  the  indi- 
vidual. In  the  simpler  organisms  the  morphological  definiteness 
is  often  less  conspicuous,  both  the  structure  and  the  behavior  being 
more  susceptible  of  modification  by  external  factors,  but  the  mcKJi- 
fications  are  themselves  definite  and  orderly  and  are  manifestly 
not  a  direct  and  specific  effect  of  the  external  factors  which  are 
acting,  but  rather  a  reaction  of  an  individual  of  some  sort  to  an 
external  change. 

In  short,  although  we  may  attempt  to  ignore  or  deny  it.  as 
various  biologists  have  done,  the  fact  remains  that  an  ordering, 
controlling  principle  of  some  sort  exists  in  the  organic  individual. 
The  existence  of  such  a  principle  does  not.  however,  as  has  so  often 
been  asserted,  distinguish  the  living  from  the  non-living  inorganic 
individual.  In  an  electrical  or  a  magnetic  field  or  in  a  planetar>' 
system,  for  example,  we  have  individuations  of  a  definite,  orderly 
character,  though  it  is  evident  that  such  individuations  are  not 
very  similar  to  living  organisms.  The  cr\'stal  also  is  an  indi- 
viduation of  a  highly  orderly  and  definite  character,  and  the  at- 
tempt has  often  been  made  to  find  some  fundamental  similarity 
between   living  organisms  and   crystals,   but   without   any  great 

199 


200  SENESCENCE  AND  REJUVENESCENCE 

success.  The  crystal  is  fundamentally  a  physical  individuation 
among  molecules  of  like  chemical  constitution,  although  in  certain 
cases  some  heterogeneity  of  composition  occurs.  In  the  organism, 
as  the  facts  show,  individuation  is  evidently  associated  with 
chemical  activity,  and  widely  different  substances  may  enter  into 
the  constitution  of  the  individual.  The  mere  existence  of  axes  in 
both  the  organism  and  the  crystal,  which  is  one  of  the  grounds  for 
comparison,  is  no  criterion  of  essential  similarity,  for  axes  may  be 
the  expression  of  very  different  conditions  in  different  cases.  No 
adequate  evidence  for  the  identity  or  similarity  of  the  axes  of  the 
organism  and  those  of  the  crystal  has  ever  been  presented,  and 
there  is  much  evidence  to  show  that  they  are  very  widely 
different. 

Apparently  two  distinct  types  of  individuation  exist  in  the 
organic  world.  In  the  one,  which  may  be  called  the  centered  or 
radiate  type,  the  parts  are  arranged  and  their  behavior  is  integrated 
with  reference  to  a  central  region ;  in  the  other,  which  we  may  call 
the  axiate  type,  with  reference  to  one  or  more  axes.  The  radiate  type 
of  individuation  appears  most  clearly  in  the  simple  cell  and  in  the 
radiate  structures  which  arise  within  it  in  connection  with  division, 
while  the  axiate  type  is  found  both  in  cells  and  in  organisms.  More- 
over, the  two  types  of  individuation  often  appear  in  combination: 
in  the  starfish,  for  example,  the  body  as  a  whole  possesses  an  oral 
aboral  axis  in  the  direction  between  the  two  surfaces,  and  the  arms 
are  axiate  structures  with  longitudinal  and  transverse  axes,  but 
they  are  arranged  radially  about  a  central  region.  Most  unicellular 
organisms  and  most  cells  which  form  parts  of  multicellular  organ- 
isms show  indications  of  a  more  or  less  definite  and  permanent  axis 
or  axes  superimposed  upon  the  centered  activities  of  the  cell.  In 
the  organism,  as  contrasted  with  the  cell,  the  axiate  type  of  indi- 
viduation is  predominant,  and  the  axiate  organization  becomes 
increasingly  definite,  conspicuous,  and  permanent  as  individuation 
advances.  In  fact,  the  very  general  occurrence  of  an  axiation  of 
some  sort,  or  of  physiological  polarity  as  it  is  commonly  called,  is 
the  foundation  of  the  behef  widely  current  among  zoologists  that 
polarity  is  a  fundamental  characteristic  of  protoplasm.  While 
most  cells  undoubtedly  do  possess  at  least  temporary  polarity, 


INDIVIDUATION  AND  REPRODUCTION  201 

there  are  many  facts  which  indicate  that  their  polarity  is  not 
self-determined,  but  is  either  acquired  during  the  course  of  their 
existence  as  a  reaction  to  external  conditions,  or  is  merely  the 
polarity  of  the  parent  cell  persisting  in  the  products  of  division. 
Moreover,  there  are  various  activities  in  the  cell  which  are  mani- 
festly not  axiate  but  radiate,  and,  finally,  no  one  has  been  able  to 
discover  the  slightest  indication  of  polarity  in  the  fundamental 
physical  structure  or  optical  properties  of  protoplasm. 

But  the  fact  remains  that  most  organisms  possess  one  or  more 
axes,  the  axes  of  polarity  and  symmetry,  so  called,  and  that  these 
axes  are  manifestly  of  fundamental  importance  in  individuation. 
The  degree  of  physiological  coherence  and  unity  in  the  individual 
is  associated  with  the  definiteness  and  fixity  of  its  axes,  and  develop- 
ment always  proceeds  in  a  definite  and  orderly  way  with  reference 
to  whatever  axes  may  exist.  Evidently  the  axes  of  the  organism 
are  not  simply  geometrical  fictions,  but  rather  the  expression  of 
some  fundamental  factor  in  the  axiate  type  of  individuation,  a 
factor  which  influences  the  rate  and  character  of  the  metabolic 
reactions  and  so  plays  an  essential  part  in  both  morphogenesis  and 
functional  activity. 

In  the  more  complex  organisms  a  polarity  and  symmetry  of  the 
whole  organism  often  exist  at  the  same  time  with  a  multitude  of 
polarities  and  symmetries  of  various  parts,  organs,  and  cells 
which  do  not  coincide  with  the  general  axes,  but  make  all  possible 
angles  with  them  and  may  be  widely  variable.  This  fact  makes  it 
evident  at  once  that  the  axiation  of  the  organism  as  a  whole  is  not 
simply  the  general  expression  of  the  axiation  of  its  parts.  Many 
different  polarities  and  symmetries  coexist  and  persist  independ- 
ently of  each  other,  and  yet  the  whole  course  of  development  is 
an  orderly  process  with  a  definite  result. 

These  characteristics  of  organic  individuals  are  not  satisfactorily 
accounted  for  by  the  current  theories  of  the  organism.  Whether 
we  regard  the  organism  from  the  viewpoint  of  the  corpuscular 
theories  as  an  aggregation  of  distinct,  self-perpetuating  entities, 
or  as  a  chemical  or  physico-chemical  system,  we  cannot  escaj^e  the 
necessity  of  accounting  in  some  way  for  its  definite  and  orderly 
behavior  and  for  the  very  evident  relation  in  axiate  forms  between 


202  SENESCENCE  AND  REJUVENESCENCE 

this  behavior  and  the  axes  of  polarity  and  symmetry.     Here  Ues 
the  problem  of  organic  individuation. 

From  time  to  time  parts  of  the  individual  give  rise  to  new  indi- 
viduals, in  which  either  the  original  axiation  may  persist  or  a  new 
axiation  arise.  This  is  reproduction.  In  the  case  of  gametic  or 
sexual  reproduction  the  process  is  further  comphcated  by  the  union 
of  two  nuclei,  usually  the  nuclei  of  two  highly  specialized  cells,  pre- 
ceding the  development  of  the  new  individual.  The  problem  of 
how  and  why  these  new  individuals  arise  is  the  problem  of  repro- 
duction. And,  finally,  it  is  at  once  evident  that  the  problems  of 
senescence  and  rejuvenescence  are  closely  associated  with  these 
problems  of  individuation  and  reproduction. 

During  some  fifteen  years'  study  of  reproductive  processes  in 
the  lower  animals  under  experimental  conditions  I  have  been 
brought  face  to  face  with  these  problems  and  have  attempted  to 
gain  some  insight  into  the  nature  of  the  factors  concerned  in  indi- 
viduation and  reproduction.  In  the  remainder  of  the  present 
chapter  the  theory  of  individuation  and  reproduction  which  has 
grown  out  of  this  investigation  is  outhned,  and  some  of  the  more 
important  experimental  evidence  upon  which  it  is  based  is  briefly 
stated. 

THE  AXIAL  GRADIENT 

By  means  of  the  susceptibility  method  described  in  chap,  iii, 
controlled  in  certain  cases  by  estimations  of  carbon-dioxide  pro- 
duction by  means  of  the  Tashiro  biometer  (Tashiro,  '13&),  it  has 
been  possible  to  demonstrate  the  existence  of  a  distinct  gradient 
in  rate  of  metabohc  reactions  along  the  chief  or  so-called  polar 
axis  of  axiate  animals,  so  far  as  they  have  been  investigated.'  In 
its  simple,  primary  form  this  axial  gradient  consists  in  a  more  or 
less  uniform  decrease  in  rate  of  metaboHsm  from  the  apical  or 
anterior  region  along  the  main  axis.  The  point  of  importance  is 
that  the  apical  region,  or  the  head-region  in  cases  where  a  head  is 
formed,  is  primarily  the  region  of  highest  rate  of  metabolism  and 
that  in  general  regions  nearer  to  it  have  a  higher  rate  than  regions 
farther  away.  In  some  animals,  as  for  example  in  Planar ia,  this 
gradient  persists  throughout  life  in  the  single  individual,  except 

'  Child,  '12,  '13a,  'i3&,  '14a,  '14^,  'i4f- 


INDIVIDUATION  AND  RErRODUC'TIOX  203 

for  some  temporary  changes  during  growth,  but  when  new  zooids 
arise  in  the  posterior  region  of  the  body  (see  pp.  122-25)  each 
zooid  develops  its  own  axial  gradient.  In  other  cases,  such  as  the 
segmented  worms,  where  the  body  increases  in  length  for  a  time  or 
indefinitely  by  the  addition  of  new  segments  arising  from  a  growing 
region  just  in  front  of  the  posterior  end,  the  gradient  appears  in  its 
simple  form  during  the  early  stages  of  development,  but  undergoes 
some  secondary  changes  in  the  posterior  regions  of  the  body  as  the 
new  segments  are  formed. 

Up  to  the  present  time  axial  gradients  have  been  found  in  all 
forms  examined,  which  include  among  unicellular  forms  some  ten 
species  of  ciUate  infusoria,  and  among  multicellular  forms  hydra 
and  several  species  of  hydroids  and  sea  anemones,  eight  species  of 
turbellaria,  the  developmental  stages  of  the  sea-urchin  and  starfish 
and  of  the  polychete  annelids  Nereis  and  Chactoplcriis,  several 
species  of  ohgochete  annehds  examined  by  Miss  Hyman,  the 
developmental  stages  of  two  species  of  fishes,  and  the  cleavage  and 
early  larval  stages  of  salamanders  and  frogs.  The  variety  of  forms 
examined  with  positive  results  leaves  no  doubt  that  the  axial 
metabolic  gradient  occurs  at  least  ver>'  widely  among  axiate 
animals. 

Where  definite  axes  of  symmetry  exist  there  are  indications  that 
metabolic  gradients  are  also  present  along  these  axes,  and  these 
gradients  show  a  definite  and  constant  relation  to  the  course  of 
development  with  reference  to  these  axes. 

These  metabolic  gradients  are  of  course  merely  the  expression 
of  a  general  condition  and  may  undergo  more  or  less  \ariation  in 
steepness,  i.e.,  in  the  amount  of  change  in  rate  of  metabolism  from 
level  to  level,  or  may  even  disappear  temporarily,  or  in  later  life 
permanently.  But  the  fact  that  in  each  species  gradients  exist 
which  are  characteristic  and  constant  within  certain  limits,  at 
least  during  the  earlier  stages  of  development,  is  of  the  greatest 
significance. 

In  addition  to  these  results,  obtained  chiefly  by  means  of  the 
susceptibiUty  method,  there  are  many  other  data  of  observ'ation 
and  experiment  which  point  unmistakably  to  the  existence  of 
axial   metaboHc   gradients   as   a  characteristic   feature  of   axiate 


204  SENESCENCE  AND  REJUVENESCENCE 

organisms  in  both  plants  and  animals.  At  present,  however,  it 
is  possible  to  call  attention  only  very  briefly  to  some  of  these.  It 
is,  for  example,  a  well-known  fact  that  in  those  plants  which  possess 
a  definite  physiological  and  morphological  axis  or  axes  the  apical 
region  of  the  axis  is  the  region  of  highest  rate  of  metabohsm,  and  a 
more  or  less  definite  downward  gradient  in  rate  exists  along  the 
axis,  at  least  for  a  certain  distance  from  the  apical  region.  This 
gradient  appears  in  the  rate  of  growth  at  various  levels  of  the  axis, 
in  the  precedence  in  development  of  the  lateral  buds  near  the  apical 
end  when  the  chief  growing  tip  has  been  removed,  and  in  many 
other  features  of  plant  life,  but  the  question  of  its  significance  has 
received  Httle  attention. 

As  regards  animals,  the  so-called  law  of  antero-posterior  devel- 
opment indicates  the  existence  of  a  metaboHc  gradient  along  the 
main  axis  of  the  organism  during  embryonic  development.  This 
"law"  is  merely  the  statement  of  the  observed  fact  of  embryology 
that  in  general  the  first  parts  to  become  morphologically  visible 
are  the  apical  or  anterior  regions,  and  these  are  followed  in  sequence 
by  successively  more  posterior  or  basal  parts.  In  other  words,  that 
region  of  the  egg  or  early  embryo  which  has  the  highest  rate  of 
metabohsm  gives  rise  to  the  apical  or  head-region,  which,  in  conse- 
quence of  the  higher  rate,  becomes  differentiated  in  advance  of  other 
parts,  and  these  follow  in  sequence  along  the  axis.  This  fact  of 
embryology  is  famiHar  to  every  zoologist,  and  its  significance  as  the 
expression  of  a  gradient  in  dynamic  activity  along  the  axis  cannot 
be  doubted,  although,  so  far  as  I  am  aware,  no  one  has  called  atten- 
tion to  it. 

Moreover,  other  facts  of  animal  embryology  indicate  very 
clearly  the  existence  of  symmetry  gradients.  In  the  bilaterally 
symmetrical  invertebrates,  with  ventral  nerve  cord,  including  most 
worms  and  the  arthropods,  and  particularly  in  those  forms  where 
the  egg  contains  much  yolk  so  that  the  embryo  is  more  or  less  spread 
out  upon  it,  the  ventral  and  median  regions  of  the  embryo  at  any 
given  level  of  the  body  develop  more  or  less  in  advance  of  the  dorsal 
and  lateral  regions.  In  such  forms  the  regions  which  give  rise  to 
ventral  and  median  parts  must  have  a  higher  rate  of  metabolism 
than  those  which  give  rise  to  dorsal  and  lateral  parts. 


INDIVIDUATION  AND  REPRODUCTION 


20! 


Fig.  69,  a  longitudinal 
section    near    the    median 
plane  of  the  embryo  of  a 
turbellarian  worm,  Plagio- 
stomum  girardi,  shows  very 
clearly    both    the    antero- 
posterior and  the  ventro- 
dorsal gradients.     At  this 
stage   only   the   head  and 
ventral  region  of  the  ani- 
mal are  represented  by  cell 
masses,  the  regions  where 
the  more  dorsal  structures 
will  later  develop  con- 
sisting chiefly  of  yolk. 
Moreover,  the  anterior  re- 
gion is  more  advanced  in 
development  than  any 
other  part.     Fig.  70  is  the 
embryo  of  the  earthworm. 
In  the  anterior  region  the 
body  has  attained  its  final 
form,   but   posteriorly   the 
segmentation  is  more  and 
more  limited  to  the  ventral 
region,    the    dorsal    region 
being   little   more   than  a 
yolk   sac,  and   in  the  ex- 
treme posterior  region  seg- 
ments have  not  yet  become 
visible.    In  the  arthropods 
the  relations  are  in  general 
similar.     The   embryology' 
of    other    invertebrate 
groups  indicates  more  or 
less   clearly    the  existence 
of  symmetry  gradients,  but 


'!<•   • 


/-•:; 


.-rmM 


'■'■-  *  • 


<r .  :■  ••  *  V-,-  -  ■ ' ' 


<'^:. 


0\- 


6 


".^  <'»i  ■«^<'  -'-'•.'•     * 


% 


(f: 


*  a 


Figs.  69,  70. — A.xial  developmental  gradients 
in  embn'onic  stages  of  invertebrates:  Kig.  69, 
a  somewhat  oblique,  longitudinal  (sagittal) 
section  of  the  embryo  of  a  turbellarian  worm, 
Plagioslomum  girardi;  the  cephalic  ganglia  and 
eye — at  the  left — are  advanced  in  development. 
as  is  also  the  pharynx,  but  farther  i)osteriorly 
fewer  cells  are  present;  the  ventral  (.lower) 
region  is  also  much  farther  advanced  than  the 
dorsal  (from  Bresslau,  '04);  Fig.  70,  advanced 
embryo  of  the  earthworm  Lumhriius  agn\ola: 
de\'eIopment  is  more  achanced  anteriorly  and 
ventrally  than  posteriorly  and  dorsally  (from 
Kowalewsky,  '71). 


2o6 


SENESCENCE  AND  REJUVENESCENCE 


the  axes  of  symmetry  differ  in  different  groups,  and  it  is  impossible 
to  consider  the  various  details  here. 

In  the  vertebrates  the  developmental  gradients  of  the  longi- 
tudinal and  transverse  axes  like  those  of  most  bilaterally  symmet- 
rical invertebrates,  show  a  decrease  in  rate  from  the  anterior  region 
posteriorly  and  from  the  median  region  laterally,  but  the  gradient 
along  the  dorso-ventral  axis  is  the  reverse  of  that  in  the  inverte- 
brates, the  dorsal  region  preceding  instead  of  the  ventral.     Fig.  71 


Figs.  71,  72. — Axial  developmental  gradients  in  the  fish  embryo:  in  Fig.  71  the 
embryo  consists  chiefly  of  the  median  dorsal  region,  in  which  the  nervous  system,  11s,  is 
developing;  in  Fig.  72  development  has  proceeded  laterally  and  ventrally,  the  somites 
5,  the  notochord  iic,  and  the  alimentary  canal  ac  being  present.  From  H.  V.  Wil- 
son, '89. 

represents  a  transverse  section  of  a  fish  embryo  at  an  early  stage  of 
development.  At  this  stage  the  embryo  consists  chiefly  of  the 
embryonic  nervous  system  (ns) ,  the  other  parts  being  represented 
by  only  a  few  cells.  Ventral  to  the  embryo  is  a  very  large  mass  of 
yolk,  not  shown  in  the  figure.  Here  the  median  dorsal  region  pre- 
cedes lateral  and  ventral  regions  in  morphogenesis.  Fig.  72  shows 
a  later  stage  in  which  morphogenesis  has  advanced  both  laterally 
and  ventrally  from  the  median  dorsal  region.     The  development 


INDIVIDUATION  AND  REPRODUCTION  207 

of  the  chick  is  essentially  similar.  Fig.  73  is  from  a  transverse 
section  of  a  very  early  stage  in  which  cells  from  what  will  later 
become  the  median  dorsal  region  are  separating  from  the  outer 
ectodermal  layer  to  form  the  mesoderm.  Somewhat  later  the 
central  nervous  system  arises  by  an  infolding  of  the  ectoderm, 
beginning  at  the  anterior  end  and  proceeding  posteriorly  in  this 
same  region.  In  Fig.  74,  a  more  advanced  stage,  the  embr>'onic 
nervous  system  is  already  present  in  the  form  of  the  neural  tube, 
and  it  is  evident  that  morphogenesis  is  proceeding  both  laterally 
and  ventrally  from  the  median  dorsal  region.  The  developmental 
gradient  along  the  longitudinal  axis  is  also  indicated  by  Figs.  73 
and  74,  for  both  are  from  the  same  embryo,  the  latter  from  a  more 
anterior,  the  former  from  a  more  posterior,  level  of  the  body.  The 
more  posterior  level  has  only  attained  the  stage  of  Fig.  73.  while 
the  more  anterior  level  has  passed  far  beyond  this  stage. 

Particular  parts  and  organs  of  the  individual  very  often  possess 
an  axis  or  axes  of  their  own  and  without  any  uniform  relation  to  the 
axis  of  the  body  as  a  whole.  Although  but  little  attention  has  been 
paid  to  this  point,  there  are  many  facts  which  indicate  that  meta- 
bohc  gradients  exist  along  these  axes,  at  least  in  the  earlier  stages 
of  development. 

In  many  animals  the  chief  axial  gradient  along  the  longitudinal 
axis  and  often  also  the  symmetry  gradients  persist  throughout  life 
or  disappear  only  in  advanced  stages  of  development.  In  fact, 
as  will  appear  below,  the  continued  existence  of  the  individual  in 
the  lower  organisms  is  dependent  upon  the  persistence  of  the 
gradients.  In  higher  forms  where  agamic  reproduction  from  pieces 
of  the  body  does  not  occur  it  is  possible  that  in  the  adult  the  gradi- 
ents may  be  altered  or  eUminated  without  altering  the  individuation 
to  any  marked  degree. 

The  axial  gradients  arise  in  various  ways  which  cannot  be  con- 
sidered in  detail  here,  but  the  different  Unes  of  evidence  indicate  that 
in  the  final  analysis  they  result  from  the  differential  action  of  factors 
external  to  the  protoplasm,  cell,  or  cell  mass  concerned.  We  see 
gradients  arising  in  nature  in  this  way,  and  it  is  possible  to  produce 
them  experimentally  by  these  means.  In  many  cases  of  the  rect)n- 
stitution  of  pieces   into   new  individuals  the  stimulation  of  the 


208 


SENESCENCE  AND  REJUVENESCENCE 


1!  ^'^ 


1 

Figs.  73,  74. — Axial  developmental  gradients  in  the  chick  embryo:  Fig.  73, 
showing  the  formation  of  the  mesoderm,  is  from  the  posterior  region  of  the  same 
embry'o  as  Fig.  74,  from  a  more  anterior  region,  in  which  morphogenesis  has  extended 
both  laterally  and  ventrally  from  the  mid-dorsal  region.  From  embryological  prep- 
arations of  the  University  of  Chicago. 


INDIVIDUATION  AND  REPRODUCTION  209 

region  adjoining  the  wound  determines  the  origin  and  direction  of 
a  new  gradient  and  so  the  axis  of  a  new  individual.  In  many 
cases  also  the  origin  and  direction  of  the  new  gradient  may  Ije 
controlled  and  determined  experimentally  in  other  ways.  Undoubt- 
edly, after  it  is  once  established  a  gradient  may  often  persist  from 
one  individual  to  another  through  the  process  of  reproduction, 
but  there  are  no  adequate  grounds  for  believing  that  such  gradients 
are  fundamental  properties  of  protoplasm,  although,  on  the  other 
hand,  it  is  probable  that  no  cell  or  cell  mass  can  exist  for  any 
great  length  of  time  in  any  natural  environment  without  acquir- 
ing, at  least  temporarily,  one  or  more  gradients,  because  external 
conditions  at  different  points  of  its  surface  can  never  remain  uni- 
form. In  general  it  may  be  said  that  the  axial  gradients  of  an 
organism  are  either  the  parental  gradients  persisting  in  the  organ- 
ism, as  in  many  cases  of  fission,  or  that  they  are  produced  de  novo 
by  conditions  which  determine  different  rates  of  metabolism  in 
different  parts  of  the  cell  or  cell  mass  at  some  stage  of  its  existence. 

The  essential  feature  in  the  estabHshment  of  a  gradient  in  meta- 
bolic rate  in  living  protoplasm  is  the  establishment  of  the  region 
of  highest  rate.  If  such  a  region  is  established  in  an  undiffer- 
entiated cell  or  cell  mass,  a  more  or  less  definite  gradient  in  rate, 
extending  to  a  greater  or  less  distance  from  this  region,  arises 
because  the  changes  in  the  primary  region  spread  or  are  trans- 
mitted, but  with  a  decrement  in  intensity  or  energy,  so  that  at  a 
greater  or  less  distance  they  become  inappreciable.  In  this  way 
the  region  of  highest  rate  becomes  the  chief  factor  in  determining 
the  rate  of  other  regions,  and  since  the  rate  thus  determined  is 
higher  in  regions  nearer  to  it  and  lower  in  those  farther  away,  a 
gradient  in  rate  results.  In  its  simplest  form,  then,  the  gradient 
may  arise  merely  from  the  spreading  or  transmission  of  metaboUc 
changes  from  the  region  of  highest  rate. 

If  metabohc  gradients  are  characteristic  features  of  the  axes  in 
living  organisms,  the  question  at  once  arises  whether  the  axis  in 
its  simplest  terms  is  anything  more  than  such  a  gradient.  In  other 
words,  are  not  physiological  and  morphological  polarity  and 
symmetry  primarily  the  expression  of  gradients  in  rate  of  metab- 
olism ?     At  present  it  can  only  be  said  in  answer  to  this  question 


2IO  SENESCENCE  AND  REJUVENESCENCE 

that  there  is  much  evidence  in  favor  of  this  view  and  none  which 
seriously  conflicts  with  it.  But  whatever  their  relation  to  polarity 
and  symmetry,  the  metaboHc  gradients  are  fundamental  factors 
in  individuation,  as  the  following  sections  will  show. 

DOMINANCE    ANTD    SUBORDINATION    OF    PARTS    IN    RELATION    TO    THE 

AXIAL    GRADIENTS 

The  process  of  experimental  reproduction  in  the  lower  animals, 
that  is,  the  development  of  new  individuals  or  parts  of  individuals 
from  pieces  cut  from  the  bodies  of  other  individuals,  affords  an 
insight  into  the  problem  of  individuation  which  cannot  be  obtained 
in  any  other  way.  In  many  of  these  cases  of  experimental  repro- 
duction a  new  individuation  takes  place  under  such  conditions  that 
it  is  possible  to  learn  something  of  the  manner  in  which  it  occurs. 
A  few  of  the  more  important  points  which  have  been  established 
are  briefly  considered  here. 

Apical  regions  or  heads  may  arise  and  develop  in  complete 
independence  of  any  other  part  of  the  body,  but  other  levels  along 
the  main  axis  can  arise  only  in  connection  with  an  apical  or  head 
region,  or  in  its  absence  with  some  region  representing  a  more 
apical  or  anterior  level.     A  few  examples  will  make  the  point  clear. 

In  its  simple,  unbranched  form  the  hydroid  Tubularia  consists 
of  the  parts  indicated  in  Fig.  75,  at  the  apical  end  the  hydranth 
with  its  two  sets  of  tentacles  and  the  reproductive  organs  between 
them,  below  this  a  long  stem,  and  in  contact  with  the  substratum 
a  stolon.  Isolated  pieces  of  the  stem  more  than  two  or  three 
millimeters  in  length  produce  a  hydranth  at  the  distal  end  and  a 
second  hydranth  may  arise  later  at  the  proximal  end  (Fig.  76),  this 
second  hydranth  being  the  result  of  a  reproductive  process  similar 
to  that  occurring  in  this  species  in  nature  (see  p.  220).  But  when 
the  pieces  are  below  a  certain  length,  which  varies  with  different 
regions  of  the  body  and  different  animals  and  also  with  different 
external  conditions,  they  give  rise  to  hydranths  or  apical  regions  of 
hydranths  at  one  or  both  ends  with  more  or  less  complete  absence 
of  other  parts.  In  the  longer  pieces  of  this  sort  a  short  stem  may 
be  formed  (Figs.  77,  78),  in  slightly  shorter  pieces  single  or  double, 
or  more  properly  biaxial  hydranths  both  complete  in  all  respects 
(Figs.  79,  80),  or  a  biaxial  structure  like  Fig.  81  with  one  complete 


INDIVIDUATION  AND  REPRODUCTION 


211 


hydranth  and  another  consisting  of  only  the  more  apical  portions 

(Fig.  8i).     In  still  shorter  pieces  the  proboscis  with  the  sex  organs, 

short   tentacles,    and    mouth 

may  appear  in  single  or 

biaxial    form    without   any 

vestiges  of  other  parts  (Figs. 

82,   St,).     And,    finally,   very 

short  pieces  give  rise  only  to 

single  biaxial  apical  portions 

of  the  proboscis  with  mouth 

and    short    tentacles     (Figs. 

84,  85). 

Whether  the  short  pieces 
produce  single  or  biaxial 
structures,  it  is  at  once  evi- 
dent that  the  more  apical 
regions  of  the  tubularian 
body,  i.e.,  the  hydranth,  or 
the  apical  regions  of  the 
hydranth,  can  develop  from 
any  piece  of  the  stem  quite 
independently  of  the  presence 
of  any  other  part  of  the  body. 
The  conditions  necessary  for 
the  development  of  these 
parts  are  present  in  each 
piece,  and  the  absence  of 
the  stem  or  even  the  basal 
portion  of  the  hydranth 
makes  no  essential  difference 
in  the  result.  The  occurrence 
of  the  biaxial  structures  is  as 
a  matter  of  fact  an  inci- 
dental result  of  the  shortness 
of  the  pieces.  In  such  pieces 
the    rate    of    metaboHsm    at 


lb 


">i 


Figs.  75,  76. — Tubularia:  Fig.  75,  a  single 
individual;  Fig.  76,  reconstitution  in  a  long 
piece  of  stem. 


the  two  ends  is  often  practically  the  same  because  they  repre- 
sent   only    a    very    small    fraction    of    the  whole  axial  gradient. 


212 


SENESCENCE  AND  REJUVENESCENCE 


Figs.  77-85.— Different  results  of  reconstitution  in  short  pieces  of  the  stem  of 
Tubularia,  showing  that  the  formation  of  the  apical  region  is  independent  of  other 
parts. 


INDIVIDUATION  AND  REPRODUCTION 


213 


Consequently  the  two  ends  react  with  equal  rapidity,  and  be^in 
development  at  the  same  time,  and  neither  becomes  dominant 
over  the  other.' 

Short  pieces  of  this  character  have  never  been  known  to 
undergo  transformation  into  stolons  or  stems  without  hydranths. 
A  stolon  or  a  stem  develops  only  in  connection  with  a  hydranth,  or 
with  a  piece  of  stem  or  stolon,  and  as  an  outgrowth  from  it.  In 
other  hydroids  and  in  coelenterates  in  general,  as  far  as  they  have 
been  examined,  the  same  relations  obtain.  The  apical  region  can 
arise  independently  of  other  parts,  but  stems  and  stolons  arise 
only  in  connection  with  other  parts  and  more  specifically  with 
parts  which  represent  physiological  regions  nearer  the  apical  end, 
rather  than  with  those  to  which  they  give  rise. 

In  the  flatworms  we  find  similar  relations  of  parts.  Short 
pieces  from  the  body  of  Planaria,  for  example,  may  develop  into 
single  or  biaxial  heads  without  any  other  part  of  the  body.  The 
head  of  Planaria  when  separated  from  the  body  by  a  cut  at  the 
level  a  in  Fig.  86  may  develop  a  head  on  its  cut  surface,  as  in  Fig. 
87;  and  short  pieces  from  other  regions,  such  as  the  piece  be  in 
Fig.  86,  may  give  rise  to  single  heads  like  Figs.  88  and  89,  or  some- 
times to  biaxial  heads  with  a  short  anterior  body  region  between 
them,  like  Fig.  90.  Evidently  development  of  a  head  from  a  piece 
is  possible,  even  in  the  complete  absence  of  other  parts  (Child,  '11b). 

In  Planaria,  as  in  Tubularia,  posterior  regions  do  not  arise 
independently  of  other  parts,  but  always  in  connection  with  regions 
which  are  more  anterior.  Any  piece  of  the  planarian  body  is  ca- 
pable of  giving  rise  to  all  parts  posterior  to  its  own  level,  whether  a 
head  is  present  or  not  (Fig.  91),  but  no  piece  is  capable  of  producing 
any  part  characteristic  of  more  anterior  levels  than  itself,  unless  a 
head  begins  to  form  first.  This  point  is  illustrated  by  F'igs.  91 
and  92.  These  pieces  represent  the  region  i J  in  Fig.  86.  When  such 
pieces  remain  headless,  as  in  Fig.  91 ,  no  changes  occur  at  the  anterior 
end  except  the  slight  growth  of  new  tissue,  the  piece  does  not  give 
rise  to  a  new  pharynx,  nor  does  the  more  anterior  region  undergo 
transformation  into  a  prepharyngeal  region.  At  the  posterior  end. 
however,    a    large    outgrowth    occurs    which    slowly    attains    the 

'  See  Child,  '07a,  b,  c,  'iia,  pp.  101-19. 


214 


SENESCENCE  AND  REJUVENESCENCE 


86 


Figs.  86-93. — Reconstitution  in  short  pieces  of  Planaria  dorotocephala:  Fig.  86, 
body-outline,  indicating  levels  of  section;  Figs.  87-89,  biaxial  and  single  heads  formed 
independently  of  other  parts;  90,  biaxial  form  with  partial  body;  Fig.  91,  headless 
piece  without  reconstitutional  changes  in  the  anterior  region;  Fig.  92,  anophthalmic 
form  in  which  anterior  region  has  undergone  reconstitution  into  the  anterior  and 
middle  body-region  of  a  whole  worm;  Fig.  93,  biaxial  tails. 


INDIVIDUATION  AND  REPRODUCTION 


215 


characteristic  structure  of  a  posterior  end.  Under  certain  conditions 
short  pieces  give  rise  to  biaxial  posterior  ends,  as  in  Fig.  93.  Morgan 
('04)  has  also  described  biaxial  posterior  ends  from  Planaria  sim- 
plicissima.  But  when  such  pieces  give  rise  to  a  head,  even  though 
it  is  of  the  rudimentary,  anophthalmic  type  of  Fig.  92,  a  new  pharj^nx 
and  mouth  arise  and  the  anterior  region  becomes  structurally  and 
functionally  a  prepharyngeal  region,  as  the  change  in  the  intestinal 
branches  in  Fig.  92  indicates.  In  some  way  all  the  changes  in  the 
piece  which  concern  the  development  of  parts  anterior  to  its  own 
level  are  dependent  upon  the  presence  of  a  head,  or,  more  correctly, 
of  a  head-forming  region. 

It  has  also  been  shown  (Child,  '13a,  '14b,  '14c)  that  the  develop- 
ment of  a  head  on  a  piece  of  the  planarian  body  is  not  the  replace- 
ment of  a  missing  part  under  the  influence  of  other  parts  of  the 
piece,  but  that  head  formation  takes  place,  if  it  takes  place  at  all, 
in  spite  of  the  remainder  of  the  piece.  The  more  vigorous  the 
other  regions  of  the  piece,  i.e.,  the  higher  their  rate  of  metabolism, 
the  less  likely  is  the  piece  to  give  rise  to  a  new  head,  and  vice  versa. 
On  the  other  hand,  the  higher  the  rate  in  a  piece,  the  more  likely  it 
is  to  produce  a  posterior  end.  In  short,  the  development  of  a  new 
individual  from  such  pieces  of  Planaria  is  essentially  the  same  pro- 
cess as  the  development  of  an  individual  from  the  egg.  It  begins 
with  the  formation  of  a  head,  and  the  head-region  in  some  way 
determines  the  reconstitution  of  certain  parts  of  the  piece  into 
more  anterior  parts,  while  other  parts  persist  with  more  or  less 
change  in  size  and  proportion  as  corresponding  parts  of  the  new 
animal.  In  the  absence  of  a  head-region  any  level  of  the  body 
controls  and  determines  the  development  of  all  more  posterior 
levels.  Much  evidence,  largely  as  yet  unpubUshed,  indicates  that 
similar  relations  exist  in  other  forms  where  the  development  of  whole 
animals  from  headless  pieces  occurs. 

These  facts  force  us  to  the  conclusion  that  in  such  experimental 
reproductions  there  is  a  relation  of  dominance  and  subordination 
of  parts.  The  apical  or  head-region  develops  independently  of 
other  parts  but  controls  or  dominates  their  development,  and  in 
general  any  level  of  the  body  dominates  more  posterior  or  basal 
levels  and  is  dominated  by  more  anterior  or  apical  levels. 


2i6  SENESCENCE  AND  REJUVENESCENCE 

It  is  a  well-known  fact  that  a  similar  relation  of  dominance  and 
subordination  exists  in  plants,  the  apical  region  or  growing  tip  of 
an  axis  being  the  dominant  or  controlhng  region  of  that  axis.  The 
"law"  of  antero-posterior  development  in  animals  suggests  that 
the  relations  are  at  least  primarily  the  same  in  embryonic  develop- 
ment as  in  experimental  reproduction.  The  cases  of  apparent 
mutual  independence  of  different  regions  or  parts  of  the  embryo 
represent  beyond  question  a  secondary  condition,  so  far  as  the 
independence  shall  prove  to  be  real. 

As  regards  the  longitudinal  axis  of  the  organism,  then,  the 
region  of  highest  rate  of  metabolism  dominates  other  regions  in  the 
earher  stages  of  development,  and  in  general  any  region  of  higher 
rate  dominates  regions  of  lower  rate.  The  developmental  gradients 
along  the  axes  of  symmetry  mentioned  above  (pp.  204-7)  suggest 
the  existence  of  a  dominance  and  subordination  along  these  axes  also. 

The  remarkable  parallelism  between  the  relations  of  dominance 
and  subordination  and  the  relations  of  metabolic  rate  along  the 
axis  suggests  that  dominance  and  subordination  may  depend  pri- 
marily on  rate  of  metabolism.  As  regards  the  plants,  it  is  evident 
that  dominance  depends  on  metabolic  activity,  for  the  effect  on 
other  parts  of  decreasing  or  inhibiting  the  metabolism  of  the  grow- 
ing tip  without  killing  it,  for  example,  by  inclosure  in  plaster  or  in 
an  atmosphere  of  hydrogen,  is  the  same  as  that  of  killing  it,  or 
removing  it  completely.  In  other  words,  the  reproduction  or 
development  of  other  growing  tips  which  was  previously  inhibited 
now  proceeds.  McCallum  ('05)  has  demonstrated  very  clearly 
that  this  relation  of  dominance  and  subordination  in  plants  is  not 
dependent  upon  nutrition,  water-content,  or  other  more  or  less 
incidental  and  widely  varying  conditions,  but  that  it  is  a  physio- 
logical correlation  of  some  sort  apparently  dependent  upon  funda- 
mental factors  in  the  plant  constitution.  As  regards  animals  also, 
there  are  many  facts,  some  of  which  will  be  considered  below,  which 
indicate  clearly  that  dominance  and  subordination  of  parts  in  the 
individual  are  primarily  dependent  upon  rate  of  metabolism,  al- 
though with  the  development  of  a  highly  irritable  conducting  sys- 
tem between  dominant  and  subordinate  parts,  such  as  the  nervous 
system,  it  is  conceivable  that  other  factors  may  play  a  part. 


IXDIVIDUATIOX  AND  REPRODUCTION  217 

THE  NATURE  AND  LIMITS  OF  DOMINANCE 

As  regards  the  nature  of  the  influence  of  the  dominant  region 
upon  other  parts,  the  physico-chemical  theory  of  the  organism 
affords  two  alternatives.  Physiological  correlation  in  the  organism, 
the  influence  of  one  part  upon  another,  so  far  as  it  is  not  directly 
mechanical,  is  accomplished  in  two  ways:  by  the  production  and 
transportation  of  substances,  commonly  known  as  chemical  corre- 
lation, and  by  the  transmission  through  the  protoplasm  in  general, 
or  along  specialized  conducting  paths,  of  excitations  which  have 
often  been  regarded  as  electrical  in  nature,  but  which  now  appear 
to  be  associated  with  chemical  changes  (Tashiro,  '13a).  If  chemical 
correlation  is  the  basis  of  the  influence  of  the  dominant  region  on 
other  parts,  then  we  must  suppose  that  metaboHsm  in  the  dominant 
region  gives  rise  to  certain  chemical  substances  which  are  trans- 
ported in  some  way  through  the  body,  but  are  gradually  used  up  or 
transformed  so  that  their  effects  cease  at  a  certain  distance  from 
the  region  of  origin.  We  may  assume,  further,  that  different  sub- 
stances are  transported  at  different  rates  or  are  completely  used  up 
at  different  distances  from  the  point  of  origin.  On  the  other  hand, 
the  dominance  and  subordination  of  parts  may  conceivably  be 
accomplished  by  transmitted  impulses.  On  the  basis  of  this 
alternative  the  metabolic  activity  of  the  dominant  region  must 
produce  certain  changes  or  excitations  which  are  transmitted 
through  the  protoplasm,  but  which  decrease  in  energy  or  effective- 
ness as  they  are  transmitted,  so  that  finally  a  limit  is  reached  beyond 
which  they  are  ineffective. 

Many  facts  favor  the  second  alternative.  In  the  first  place, 
chemical  substances  may  be  transported  to  any  distance  in  the 
fluids  of  an  organism,  and  it  is  difiicult  to  see  how  any  definite  and 
characteristic  limit  of  effectiveness  of  such  substances  could  exist, 
unless  we  could  assume  that  they  were  difi"using  through  a  homoge- 
neous medium  or  being  transported  at  a  definite  rate  and  under- 
going destruction  also  at  a  definite  rate  during  transportation. 
But  it  is  certain  that  neither  of  these  possibiUties  is  realized  in  all 
organisms  in  which  a  limit  of  effectiveness  of  dominance  ajipears, 
and  it  is  a  fact  that  the  existence  of  a  decrement  and  a  limit  of 
effectiveness  in  transmission  has  been  obser\-ed   in   nian>-  cases 


2i8  SENESCE^XE  AND  REJUVENESCENXE 

among  both  plants  and  animals,  and  for  excitations  transmitted 
through  the  general  protoplasm,  as  well  as  those  transmitted 
through  muscle  and  nerve/  In  some  of  the  lower  animals  the 
gradual  fading  out,  with  increasing  distance  from  the  point  of 
origin,  of  the  muscular  contractions  following  a  slight  local  stimu- 
lation, affords  a  visible  demonstration  of  the  decrease  in  effective- 
ness with  transmission,  and  the  relation  between  the  distance  from 
the  point  of  stimulation  at  which  the  contraction  ceases  to  occur 
and  the  strength  of  stimulation  indicates  further  that  the  more 
intense  excitation  is  transmitted  to  a  greater  distance  than  the  less 
intense.  And,  finally,  there  can  be  no  doubt  that  impulses  may  be 
transmitted  to  greater  distances  over  speciahzed  conducting  paths, 
of  which  nerves  are  the  most  highly  developed  form,  than  through 
the  general  protoplasm,  and  apparently  some  nerves  conduct  with 
less  decrement  per  unit  of  distance  than  others. 

Certain  physiologists  maintain  that  the  medullated  nerves  of 
vertebrates  conduct  impulses  without  any  decrement.  If  this  is 
true,  an  impulse  might  be  transmitted  in  such  a  nerve  to  an  in- 
finite distance  from  its  point  of  origin.  There  are,  however,  certain 
facts  which  indicate  that  even  in  these  nerves  a  decrement  does 
occur  in  the  course  of  transmission,  although  it  is  often  so  slight  as 
to  be  inappreciable  under  ordinary  conditions  in  the  relatively  short 
pieces  of  nerves  usually  available  for  experiment.  In  the  first  place, 
the  electrical  change,  the  negative  variation  accompanying  the 
passage  of  a  nerve  impulse,  has  been  shown  to  undergo  decrease 
with  increasing  distance  from  the  point  of  stimulation,  and  the 
effectiveness  of  the  impulse  in  producing  muscular  contraction 
decreases  in  the  same  way.  Moreover,  various  investigators  have 
recorded  the  existence  of  a  decrement  in  the  intensity  of  the  impulse 
in  partially  anaesthetized  nerves,  and  there  is  no  reason  to  believe 
that  the  partial  anaesthesia  alters  the  fundamental  nature  of  the 
nerve  as  conductor:  in  all  probability  it  merely  makes  the  nerve  a 
less  efi&cient  conductor,  so  that  the  decrement  becomes  apparent 


'  For  general  consideration  of  the  whole  subject  of  conduction  see  Fitting,  'o 
for  plants,  especially  pp.  91-93  and  122-24;  Biedermann,  03,  especially  pp.  204-S, 
and  Verworn,  '13,  chap.  vi.  for  animals.  See  also  Boruttau,  '01;  Ducceschi,  '01; 
A.  Fischer,  '11;   Kretzschmar,  '04;  Lodholz,  'i.^. 


INDIVIDUATION  AND  REPRODUmON  219 

within  a  shorter  distance  than  in  the  normal  nerve.  It  is  inij^os- 
sible  to  consider  the  literature  of  this  much-discussed  problem  here, 
but  it  may  be  said  that  there  is  considerable  evidence  which  indi- 
cates that  a  decrease  in  energy  or  effectiveness  occurs  in  the  course 
of  transmission,  even  in  the  most  highly  developed  nerve  fibers, 
while,  up  to  the  present  time,  no  one  has  actually  demonstrated 
that  conduction  without  decrement  over  any  considerable  distance 
occurs.  It  appears,  then,  that  transmitted  excitations  in  organisms 
do  in  general  show  a  more  or  less  rapid  decrement  and  conse- 
quently a  limit  of  effectiveness  at  a  greater  or  less  distance  from  the 
point  of  origin.  In  other  words,  such  excitations  gradually  die 
out  like  a  wave  or  an  electric  impulse,  but  the  more  intense  the 
excitations  or  the  better  the  conducting  path,  the  greater  the  dis- 
tance between  point  of  origin  and  limit  of  effectiveness.  From  our 
knowledge  of  conduction  of  excitations  in  non-living  substances, 
this  is  what  we  should  expect  in  conduction  in  living  substance. 

If  the  dominance  of  one  region  over  another  in  the  organism 
depends  upon  such  transmitted  excitations,  there  must  be  a  spatial 
limit  to  such  dominance.  And  since  the  excitations  which  proceed 
from  the  dominant  region  must  result  from  metabolic  changes 
occurring  there,  we  should  expect  to  find  them  varj-ing  in  intensity 
with  the  rate  of  metabolism  in  the  dominant  part.  Moreover,  the 
more  intense  the  excitation  and  the  better  the  conductor  through 
which  the  excitation  is  transmitted,  the  greater  its  effective  range, 
i.e.,  the  distance  to  which  it  can  travel  before  becoming  ineffective. 
Consequently  the  spatial  limit  of  dominance  must  var}'  with  the 
rate  of  metabohsm  in  the  dominant  part  and  the  efficiency  of  the 
conducting  path  between  that  and  other  parts.  In  the  plants  and 
lower  animals  and  in  early  stages  of  embryonic  development  of  all 
forms  the  efficiency  of  conduction  is  low  and  dominance  is  in  general 
effective  over  rather  limited  distances.  In  the  later  stages  of 
development  of  those  forms  which  possess  a  nervous  system  the 
efficiency  of  conduction  increases  very  greatly  as  the  nerves 
develop,  and  the  spatial  limit  of  dominance  likewise  increases  ver}' 
greatly. 

In  the  plants  and  lower  animals  the  limit  of  dominance^  is  indi- 
cated very  clearly  by  the  size  of  the  individual  or  part  concerned. 


220 


SENESCENCE  AND  REJUVENESCENCE 


and  growth  beyond  this  size  results  in  the  formation  of  a  new  indi- 
vidual or  individuals  from  some  part  of  the  old,  that  is,  in  some  form 

of  reproduction.  The  repetitive  development  in 
series  of  parts,  such  as  node  and  internode,  in 
the  stem  of  the  plant,  of  segments  in  segmented 
animals,  and  many  other  cases,  are  examples  of 
similar  relations  between  parts.  The  organic 
individual  in  fact  exhibits  a  more  or  less  definite 
sequence  of  events  in  space  as  well  as  in  time, 
and  it  is  impossible  to  doubt  that  a  physiological 
spatial  factor  of  some  sort  is  concerned.  This 
problem  has  been  considered  at  some  length  in 
an  earlier  paper  (Child,  'iia),  and  only  brief 
mention  of  some  of  the  important  points  is 
possible  here. 

In   the   simpler   cases   of   reproduction  the 
spatial  factor  in  dominance  is  clearly  evident  in 
the  position  of  the  part  concerned  in  reproduc- 
tion with  respect  to  the  original  dominant  region. 
In  Tubularia  (Fig.  75,  p.  211),  for  example,  the 
stem  and  stolon  increase  in  length,  and  when 
a  certain  length,  varying  with  conditions  which 
affect  rate  of  metabolism,  is  attained,  the  tip  of 
the  stolon  turns  upward  away  from  the  sub- 
stratum and  gives  rise  to  a  hydranth,  as  in  Fig. 
94.     This  hydranth  and  its  stem  grow  in  turn; 
a  stolon  arises  from  the  base,  and  when  a  cer- 
tain length 
of  stem  plus 
stolon     is 
reached,  the 
process    of 
reproduc- 
tion is   then 
repeated. 


Fig.  94. — The  primary  form  of  agamic  reproduction  in  Tubularia 


Evidently  the  stolon  tip  gives  rise  to  a  hydranth  only  when  it  has 
attained   a   certain   distance   from    the   original   hydranth.     The 


INDIVIDUATION  AND  REPRODITTIDX 


221 


formation  of  a  hydranth  at  the  basal  end  of  pieces  of  the  stem  t)f 
Tubularia  under  experimental  conditions  (Fig.  76,  p.  211)  is  simply 
the  same  reproductive  process  which  occurs  in  nature,  except  that 
under  the  experimental  conditions  it  occurs  in  a  shorter  length  of 
stem  because  the  rate  of  metabolism  is  lower.  In  Planaria  and 
other  fiatworms  which  undergo  fission  the  body  attains  a  certain 
length  and  then  the  posterior  region  becomes  a  new  zooid,  as  de- 
scribed in  chap.  vi.  The  length  which  the  individual  attains 
can  be  widely  varied  and  controlled  by  experimental  conditions 
which  affect  the  rate  of  metabolism  (Child,  'iic). 


Fig.  95. — Reproduction  of  new  plants  from  runners  in  the  strawberry.     From 
Seubert,  '66. 


In  plants  similar  relations  are  of  very  general  occurrence.  In 
the  strawberry  plant,  for  example  (see  Fig.  95),  the  runner  attains 
a  certain  length  before  the  growing  tip  gives  rise  to  a  new  plant, 
but  by  cutting  off  or  inhibiting  the  metabolism  of  the  growing  tip 
of  the  parent  plant  the  development  of  a  new  plant  at  the  tip  of 
the  runner  can  be  induced  at  any  time.  These  few  cases  will  serve 
to  call  to  mind  many  others  among  both  plants  and  animals  in 
which  a  spatial  factor  and  a  limit  of  effectiveness  of  the  dominance 
of  the  apical  or  head-region  is  evident. 

Within  the  limits  of  the  individual  organism  the  same  factor 
appears  in  the  length  and  position  of  various  parts,  and  it  has  been 


222 


SENESCENCE  AND  REJUVENESCENCE 


shown  elsewhere  (Child,  iib)  that  in  Planaria  the  spatial  relations 
of  parts  can  be  altered  experimentally  by  altering  the  rate  of 
metaboHsm  in  the  dominant  head-region.  For  example,  a  piece  of 
Planaria  including  any  considerable  portion  of  the  postpharyngeal 
region  such  as  he,  Fig.  86  (p.  214),  when  allowed  to  undergo  recon- 
stitution  in  water  at  room  temperature,  forms  an  animal  which  in 


Figs.  96-100. — Reconstitution  of  similar  pieces  of  Planaria  dorotoccphala  under 
different  conditions,  to  show  different  positions  of  pharynx  and  lengths  of  prepharyn- 
geal  region:  Fig.  96,  reconstitution  in  well-aerated  water  at  20°  C;  Figs.  97-99> 
different  degrees  of  reconstitution  in  weak  solutions  of  narcotics;  Fig.  100,  reconsti- 
tution in  well-aerated  water  at  28°  C. 

its  earUer  stages  is  like  Fig.  96.  The  new  pharynx  and  mouth 
appear  anterior  to  the  middle  of  the  piece  at  a  certain  characteristic 
distance  from  the  head,  and  in  the  region  between  the  pharynx 
and  head  the  characteristic  structure  of  the  prepharyngeal  region 
develops.  But  if  such  pieces  undergo  reconstitution  in  weak  solu- 
tions of  alcohol,  ether,  chloretone,  or  other  anaesthetics,  or  under 


INDIVIDUATION  AND  REPRODUCTION  22? 

other  conditions  which  decrease  the  rate  of  metabolism,  the  head  is 
smaller  and  develops  more  slowly,  the  pharynx  appears  much  nearer 
the  head,  and  the  new  prepharyngeal  region  is  correspond ingh- 
shorter  (Figs.  97,  98).  In  extreme  cases  the  head  may  be  terato- 
morphic  (Fig.  99),  or  even  anophthalmic  (see  pp.  111-12J.  and 
no  reconstitution  occurs  posterior  to  it.  In  similar  pieces,  under 
conditions  which  increase  the  rate  of  metabolism,  such  as  high 
temperature,  the  prepharyngeal  region  is  longer  and  the  phar\-nx 
appears  farther  from  the  head  (Fig.  100).  Evidently  the  distance 
from  the  anterior  end  at  which  certain  conditions  arise  in  the  piece 
under  its  influence  varies  with  the  rate  of  metabolism  in  the  domi- 
nant anterior  region.  When  the  rate  is  very  low  the  anterior  region 
does  not  bring  about  any  visible  change  in  regions  posterior  to  itself, 
and  the  higher  the  rate  the  greater  the  distance  at  which  particular 
changes  occur. 

In  the  higher  animals,  such  as  the  vertebrates,  as  well  as  in  the 
higher  invertebrates,  the  size  of  the  adult  individual  is  limited  by 
other  factors  than  the  hmit  of  dominance,  so  that  such  animals 
never  attain  anything  like  what  might  be  called  the  physiological 
maximum  of  size.  The  chief  limiting  factor  in  these  cases  is 
apparently  the  higher  degree  of  differentiation  of  the  cells  which 
results  in  the  retardation  and  sooner  or  later  in  the  almost  complete 
or  complete  cessation  of  growth.  Only  in  those  forms  in  which 
agamic  reproduction  occurs  can  we  be  certain  that  the  individual 
attains  the  physiological  maximum,  i.e.,  the  size  determined  by  the 
limit  of  dominance.  In  the  adult  stages  of  the  higher  animals 
dominance  may  extend  to  almost  indeiinite  distances,  but  individual 
size  is  limited  by  differentiation  and  lack  of  capacity  for  indefinite 
or  long-continued  growth.  Even  in  these  forms,  however,  the  size 
of  parts  and  their  repetitive  reproduction  during  development  may 
be  determined  by  the  limits  of  dominance  in  the  early  stages. 

When  we  consider  all  these  facts  and  many  others,  some  of  which 
have  been  mentioned  elsewhere'  but  cannot  be  discussed  here,  wc 
are  forced  to  conclude  that  a  relation  of  dominance  and  subordi- 
nation of  parts  in  the  organism  really  exists,  that  it  is  effective 
only  within  a  certain  spatial  limit,  varying  with  conditions  in  the 

'  Child,  'iia,  'lib,  'iic,  '13a,  '146,  'i^c. 


2  24  SENESCENCE  AND  REJUVENESCENCE 

organism,  and  that  it  seems  to  depend  primarily  upon  impulses  or 
changes  of  some  sort  transmitted  from  the  dominant  region,  rather 
than  upon  the  transportation  of  chemical  substances.  Chemical 
substances  arising  in  the  course  of  metabolism  are  undoubtedly 
important  factors  in  determining  the  constitution  and  character  of 
particular  organs  and  parts,  but  it  is  difficult  to  understand  how 
they  can  account  for  the  definite  and  orderly  spatial  characteristics 
of  living  things.  Hormones,  internal  secretions,  and  other  chemi- 
cal substances  unquestionably  play  a  very  essential  role  in  physio- 
logical correlation,  particularly  in  the  higher  animals  where 
different  organs  are  highly  differentiated,  but  for  the  production  of 
such  different  specific  substances  different  organs  are  necessary. 
At  present  we  are  concerned  with  the  question  of  the  primary 
origin  of  these  organs,  with  the  appearance  and  localization  of 
differences  which  make  possible  the  production  of  different  specific 
substances  in  different  parts  of  the  individual,  and  it  is  evident 
that  these  primary  specializations  and  differentiations,  their  locali- 
zation and  orderly  and  definite  spatial  arrangement,  cannot  be 
accounted  for  by  the  action  or  interaction  of  such  substances. 

According  to  the  conception  developed  above,  the  dominance  of 
a  region  depends  primarily  upon  its  rate  of  metabolism  as  compared 
with  that  of  other  regions  within  the  range  of  its  influence.  Where 
the  region  of  high  rate  is  the  primary  factor  in  maintaining  the 
gradient,  as  it  undoubtedly  is  in  the  lower  organisms  and  in  the 
early  stages  of  development  of  many  higher  forms,  it  is  of  course 
the  chief  factor  in  determining  the  metabolic  rate  in  other  regions 
and  so  maintains  its  original  dominance.  But  in  more  highly 
differentiated  forms,  or  in  later  developmental  stages,  where  rela- 
tively permanent  structural  differentiations  have  arisen  along  the 
course  of  the  gradient,  so  that  it  has  become  structurally  fixed, 
the  region  of  highest  rate  still  remains  dominant  because  it  gives 
rise  to  more  powerful  impulses  than  do  other  regions  and  conse- 
quently influences  them  more  than  they  do  it.  Lastly,  in  the  higher 
animals,  where,  in  all  except  early  embryonic  stages,  transmission 
through  nerves  is  the  chief  factor  in  physiological  integration  (see 
Sherrington,  '06),  the  original  gradient  in  metabohc  rate  may 
persist  chiefly,  or  perhaps  in  some  cases  only,  in  the  efferent  con- 


INDIVIDUATION  AND  REPRODUCTION  225 

ducting  paths  of  the  nervous  system,  while  in  other  parts  of  the 
body  the  metabohc  rate  has  been  altered  by  various  factors. 

At  present  there  seems  to  be  no  good  reason  for  believing  that 
the  changes  or  impulses  transmitted  from  the  dominant  region 
affect  the  metabolic  processes  in  regions  which  they  reach  in  any 
other  than  a  quantitative  way.  The  dominant  region  is  not  to  be 
conceived  as  giving  rise  to  a  variety  of  different  kinds  of  impulses 
which  produce  different,  specific,  formative  effects,  but  rather 
merely  as  a  region  of  high  metabolic  rate,  from  which  changes  con- 
nected with  its  metabolic  activity  spread  or  are  transmitted  to 
other  regions  and  increase  their  metabolic  activity.  Since  these 
transmitted  changes  decrease  in  energy  or  effectiveness  with  trans- 
mission, they  must  determine  a  higher  rate  in  the  regions  nearer 
the  dominant  region  than  in  those  farther  away.  In  this  way  the 
determination  of  a  high  rate  of  metabolism  in  one  region  may  result 
in  the  establishment  of  a  metabolic  gradient  in  one  or  more  direc- 
tions from  that  region.  Each  point  along  an  axis  is  then  character- 
ized by  a  more  or  less  definite  rate  of  metabolism,  and  if  more  than 
one  axis  is  present  each  point  in  the  organism  has  a  rate  determined 
by  its  position  in  each  of  the  axial  gradients. 

From  this  point  of  view  the  axiate  individual,  whether  it  is  a 
whole  organism  or  a  part,  when  reduced  to  its  simplest  terms  con- 
sists of  one  or  more  gradients  in  rate  of  metabohsm  in  a  cell  or  cell 
mass  of  specific  constitution.  Of  course  this  condition  represents 
only  the  first  step  in  individuation.  Whether  ever>-  individual 
organism  in  every  generation  has  its  beginning  in  a  condition  as 
simple  as  this  can  be  determined  only  by  extensive  investigation. 
Certainly  other  factors,  such  as  difference  of  conditions  at  the  sur- 
face and  in  the  interior,  the  presence  of  reserve  substance  such  as 
yolk  in  certain  cells,  etc.,  play  a  part  sooner  or  later  in  many  cases. 
But  that  the  simplest  axiate  individuals  among  organisms  consist 
essentially  of  metabohc  gradients  in  a  specific  protoplasm  is  a 
conclusion  supported  by  a  large  body  of  evidence.  The  axes  of 
the  organism  or  its  parts  are,  according  to  this  view,  in  their  simjilest 
terms  nothing  but  such  gradients,  and  the  structure  of  the  apical 
region  or  head  of  the  organism  represents  merely  the  develop- 
mental result  of  a  high  rate  of  metabolism  and  independence  of 


226  SENESCENCE  AND  REJUVENESCENCE 

other  parts.  With  a  sufficiently  high  rate  of  metabohsm  and  when 
not  subordinated  to  other  parts,  any  part  of  the  simpler  organisms 
is  capable  of  developing  into  an  apical  region  or  head. 

The  objection  may  be  raised  that  even  if  such  a  metabolic 
gradient  is  established,  there  is  nothing  to  maintain  it  with  the 
necessary  degree  of  constancy  to  produce  definite  results.  As  a 
matter  of  fact,  regional  differences  in  metabolism  do  maintain 
themselves  to  a  remarkable  degree  and  may  even  be  accentuated. 
Certam  muscles  frequently  or  strongly  stimulated  become  capable 
of  greater  activity,  and  httle-used  parts  gradually  lose  their 
capacity  for  activity.  There  is  good  reason  to  believe  that  within 
certain  Hmits  an  increase  in  rate  of  metabohsm  in  a  protoplasmic 
substratum  changes  the  condition  of  the  substratum  so  that  a  still 
higher  rate  is  possible,  and  vice  versa.  The  analog>'  between  the 
organism  and  the  stream  referred  to  in  chap,  i  is  perhaps  of  service 
here.  An  increase  in  rate  of  flow  of  the  stream  alters  the  channel 
so  that  a  still  higher  rate  is  possible,  and  a  decrease  in  rate  of  flow 
produces  conditions  which  bring  about  further  decrease.  Moreover, 
the  region  of  high  rate  of  metabolism  in  the  organism  once  estab- 
lished is  more  susceptible  because  of  its  high  rate  to  the  action  of 
external  conditions:  in  animals,  particularly  in  motile  forms,  this 
region  becomes  the  seat  of  the  special  sense-organs  and  is  therefore 
the  most  important  part  of  the  body  as  regards  relations  between 
the  organism  and  the  external  world.  These  conditions  result  from 
the  original  high  metabolic  rate  of  the  region,  but  they  also  con- 
tribute toward  maintenance  of  a  relatively  high  rate  of  metabohsm. 

And,  finally,  the  question  whether  purely  quantitative  differences 
along  an  axis  are  sufficient  to  account  for  the  morphological  differ- 
ences which  arise  along  that  axis  is  one  which  can  be  answered  only 
after  the  most  extended  and  painstaking  investigation.  At  present 
we  know  that  morphological  characters  can  be  altered  very  widely 
by  conditions  whose  effect  upon  the  organism  is  primarily  quanti- 
tative. The  different  types  of  anterior  end  in  pieces  of  Planaria 
(see  pp.  111-12)  are  cases  in  point.  The  very  general  behef  that 
quaUtatively  different  substances  or  entities  of  some  kind  are 
necessary  as  a  basis  for  morphological  development  does  not  rest 
upon  direct  or  experimental  evidence,  but  is  an  inference  from  the 


INDIVIDUATION  AND  REPRODUCTION  227 

morphological  characters  themselves.  As  a  matter  of  fact  we 
know  that  even  in  relatively  simple  chemical  reactions  quantitative 
differences  may  very  often  give  rise  to  qualitatively  different  results. 
And  when  we  recognize  the  very  great  complexity  of  metabolism  in 
even  the  simplest  organism,  we  cannot  but  admit  that  there  must 
be  many  possibilities  in  the  metabolic  complex  for  the  origin  of 
qualitative  differences  in  characters,  organs,  etc.,  from  quantitative 
differences  in  metabolism.  Manifestly,  quality  and  quantity  in 
organisms  are  not  and  cannot  at  present  be  clearly  distinguished. 
That  qualitative  differences  in  the  chemical  constitution  and 
metabolism  of  different  organs  exist  is  evident,  but  there  is  at 
present  no  vaHd  evidence  that  such  differences  cannot  be  reduced 
to  a  quantitative  basis. 

DEGREES  OF  INDIVmUATIOX 

If  the  organic  individual  consists  fundamentally  of  one  or  more 
gradients  in  rate  of  metabolism  with  a  relation  of  dominance  and 
subordination  between  regions  of  higher  and  those  of  lower  rate,  it 
is  at  once  apparent  that  the  degree  of  integration  of  such  an 
individual  into  a  physiological  unit,  the  degree  of  physiological 
coherence  and  of  orderly  behavior,  must  vary  widely  with  various 
factors  of  its  constitution.  Since  it  will  often  be  necessary  in  follow- 
ing chapters  to  call  attention  to  differences  in  the  degree  of  indi- 
viduation, some  of  these  factors  must  be  briefly  considered  here. 

The  efficiency  of  conduction  is  a  most  important  factor  in 
individuation.  In  the  lower  organisms  and  in  the  embr\-onic 
stages  of  even  the  higher  animals  where  the  decrement  in  conduc- 
tion is  great,  the  degree  of  individuation  is  much  lower  than  in 
those  forms  or  stages  which  possess  a  well-developed  ner\'ous  sys- 
tem, where  the  decrement  is  much  less  or  almost  inappreciable.  In 
the  lower  forms  and  in  embryonic  stages  a  higher  metabolic  rate  is 
necessary  for  permanent  individuation;  in  other  words,  in  order  to 
become  or  remain  dominant,  a  given  level  must  have  a  higher  rate 
of  metabolism  in  relation  to  other  levels  than  when  a  nerv'ous  system 
is  present. 

Another  factor  in  individuation  is  the  physiological  stability 
of   the  structural  substratum.     The  greater  the  stability  of  the 


228  SENESCENCE  AND  REJUVENESCENCE 

substratum,  the  greater  the  possibiUties  of  speciaHzation  and  differ- 
entiation along  the  axis  in  relation  to  the  gradient  and  therefore  the 
more  intimate  and  complex  the  correlation  between  parts  and  the 
higher  the  degree  of  unity  in  the  whole.  In  the  lower  forms,  where 
structures  once  formed  may  disappear  in  a  few  hours  or  a  few 
days  under  altered  physiological  conditions,  there  is  no  possibihty 
of  such  minute  and  dehcate  interrelation  and  adjustment  of  parts 
to  each  other  as  in  the  higher  forms,  where  regressive  changes  are 
much  less  extensive.  In  fact,  the  advance  in  development  of  the 
nervous  system  itself  from  the  lower  to  the  higher  forms  is  in  part 
dependent  upon  the  increase  in  stabihty  of  the  structural  sub- 
stratum. 

The  degree  of  individuation  is  dependent  upon  the  rate  of 
metabolism.  At  any  given  stage  of  development  the  higher  the 
rate  of  metabohsm,  the  higher  the  degree  of  individuation.  But 
we  cannot  properly  compare  earher  and  later  stages  of  development 
in  this  way,  for,  although  the  rate  of  metabohsm  decreases  during 
development,  the  degree  of  individuation  increases  in  most  cases 
up  to  the  adult  stage,  because  of  the  increasing  efficiency  of  conduc- 
tion and  the  specialization  and  interrelation  of  parts.  It  is  only 
after  the  adult  stage  is  attained  that  the  further  decrease  in  meta- 
bohc  rate  with  advancing  senescence  determines  a  gradual  decrease 
in  the  degree  of  individuation,  a  physiological  disintegration. 

Many  other  incidental  and  external  factors  may  alter  the  degree 
of  individuation  in  organisms.  In  general,  depressing  factors 
decrease  and  stimulating  factors,  at  least  up  to  a  certain  Hmit, 
increase  it.  The  point  of  chief  importance  is,  however,  the  possi- 
bihty of  distinguishing  different  degrees  of  individuation  and  of 
interpreting  them  to  some  extent,  however  incompletely,  in  physico- 
chemical  terms. 

PHYSIOLOGICAL  ISOLATION  AND  AGAMIC  REPRODUCTION 

If  the  axiate  individual  consists  of  a  dominant  and  of  sub- 
ordinate parts,  the  structure,  differentiation,  and  special  function 
of  the  subordinate  parts  are  dependent,  at  least  to  a  considerable 
degree,  upon  their  relation  to  the  dominant  part.  Isolation  of  such 
parts  from  the  influence  of  the  dominant  part  must  result,  if  the 


INDIVIDUATION  AND  REPRODUCTION  229 

isolated  parts  are  capable  of  reacting  to  the  change,  first,  in  a  loss 
of  their  characteristics  as  parts,  and,  secondly,  if  conditions  permit, 
in  a  new  individuation  which  may  bring  about  the  development  of 
a  complete  new  individual  from  the  isolated  part.  In  short  the 
isolation  of  a  subordinate  part  from  the  influence  of  the  dominant 
part  is  a  necessary  condition  for  reproduction.  In  experiment 
pieces  are  physically  isolated  from  the  body  of  the  animal  by  section, 
and  in  the  lower  simpler  forms  reproduction  follows  such  isolation, 
and  the  piece  becomes  a  new  whole,  or  at  least  undergoes  changes  in 
that  direction. 

There  are  certain  features  of  the  simpler  reproductive  processes 
in  nature  which  suggest  that  in  these  cases,  as  in  the  experimental 
reproduction  of  artificially  isolated  pieces,  an  isolation  from  the 
influence  of  the  dominant  part  is  the  essential  condition  for  repro- 
duction. In  many  forms,  both  plants  and  animals,  growth  beyond 
a  certain  length  or  size,  which  is  dependent  upon  rate  of  metabolism, 
degree  of  differentiation,  etc.,  results  in  the  transformation  of  that 
portion  of  the  individual  most  distant  from  the  dominant  part  into 
a  new  individual.  The  case  of  Tuhularia  mentioned  above  (Fig.  94, 
p.  220)  is  a  good  illustration,  and  in  many  plants  similar  vegetative 
reproductions  occur.  It  is  impossible  to  doubt  that  in  such  cases 
growth  to  a  certain  size  brings  the  region  in  question  into  a  condi- 
tion where  it  is  able  to  behave  as  if  it  were  physically  isolated, 
like  a  piece  cut  from  the  body. 

It  is  also  a  fact,  however,  that  reproduction  may  occur  in  conse- 
quence of  the  weakening  or  removal  of  the  dominant  part  and  with- 
out any  preceding  increase  in  size  of  the  individual.  Such  cases 
are  very  common  among  the  plants,  where  the  removal  or  inhibition 
of  metabolism  of  the  growing  tip  of  the  main  axis  or  stem  is  fol- 
lowed by  development  of  a  new  axis  from  a  lateral  branch  or  bud. 
Very  commonly  also  the  removal  of  all  growing  tips  is  followed  by 
the  development  of  "adventitious"  growing  tips,  which  often  arise 
from  differentiated  cells  by  a  process  of  dediff erentiation  and  growth. 
Among  the  lower  animals  similar  cases  occur.  Increase  in  size  is 
not  then  a  necessary  condition  for  reproduction.  Decrease  in  rate 
of  metabohsm  or  inhibition  of  metaboUsm  in  the  dominant  region 
may  bring  about  reproduction  as  readily  as  growth. 


230  SENESCENCE  AND  REJUVENESCENCE 

The  analysis  of  the  simple  forms  of  agamic  reproduction  in 
connection  with  the  experimental  reproductions  in  artificially  iso- 
lated pieces  leaves  no  room  for  doubt  that  the  formation  of  a  new 
individual  from  a  part  of  a  pre-existing  individual  results  from  the 
removal  of  an  inhibiting  factor  rather  than  from  a  positive  stimu- 
lation. According  to  the  conception  of  the  individual  developed 
above,  a  more  or  less  complete  physiological  isolation  of  the  region 
or  part  concerned  is  a  necessary  condition  for  reproduction,  or, 
more  specifically,  this  part  must  in  some  way  escape  from  the  con- 
trol of  the  dominant  region  before  it  can  lose  its  characteristics  as 
a  part  and  so  serve  as  the  basis  for  a  new  individuation.' 

In  the  simpler  organisms,  where  isolated  parts  are  capable  of 
reconstitution  into  new  individuals,  the  effect  of  physiological 
isolation  of  a  part  is  essentially  the  same  as  that  of  physical  isola- 
tion by  section,  except  that  physiological  isolation  is  a  less  violent 
and  injurious  procedure.  The  isolated  part  undergoes  dediffer- 
entiation  to  a  greater  or  less  extent  and  begins  a  new  development, 
an  agamic  reproduction  occurs.  But  in  the  higher  forms,  where 
isolated  parts  are  incapable  of  reconstitution,  physiological  isolation 
may  lead  to  death  of  the  part  isolated,  or  if  nutrition  is  available 
the  part  may  continue  to  exist  in  its  original  form  or  to  grow 
and  differentiate  along  the  lines  previously  determined  by  its  rela- 
tions with  other  parts. 

It  is  evident  that  the  final  size  of  the  individual  is  determined  by 
the  limit  of  dominance  only  in  the  lower,  simpler  organisms.  It 
was  pointed  out  above  that  in  the  higher  animals  other  factors — ■ 
such  as  the  rapid  differentiation  and  loss  of  capacity  for  growth  and 
division  of  cells  and  perhaps  the  increasing  disproportion  between 
surface  and  volume^imit  the  individual  to  a  size  far  below  that 
which  the  Hmit  of  dominance  alone  would  determine.  If,  for  ex- 
ample, the  size  of  man  and  mammals  were  limited  only  by  the  limit 
of  effective  transmission  of  nerve  impulses  in  fully  developed  nerve 
fibers,  they  would  certainly  be  very  much  larger  than  they  are. 
In  early  embryonic  stages,  however,   the  Hmit  of  dominance  is 

'  For  experimental  data  see  Child,  '07a,  '076,  '10,  'iic,  and  for  a  general  considera- 
tion of  physiological  isolation  of  parts,  the  ways  in  which  it  is  brought  about,  and 
its  significance,  see  Child,  '11a. 


INDIVIDUATION  AND  REPRODUCTION  231 

undoubtedly  a  factor  in  determining  the  limits  of  the  individual  in 
at  least  some  mammals,  for  Patterson  ('13)  has  shown  that  the 
four  embryos  of  the  nine-banded  armadillo  are  the  result  of  agamic 
reproduction,  of  a  process  of  budding  of  the  primarily  single  embryo, 
and  suggests  that  duplicate  twins  and  double  monsters  may  arise 
in  the  same  manner. 

There  can  be  no  doubt  that  during  the  course  of  individual 
development  a  greater  or  less  degree  of  extension  of  dominance 
occurs  as  the  paths  of  transmission  develop.  In  the  early  embry- 
onic stages  the  influence  of  the  dominant  region  extends  only  a 
short  distance,  but,  particularly  in  organisms  where  a  nervous 
system  develops,  transmission  of  impulses  to  greater  distances 
becomes  possible  as  development  proceeds.  Consequently  the 
size  of  the  individual  may  increase  during  development,  in  many 
cases  very  greatly,  without  physiological  isolation  of  any  part  and 
so  without  agamic  reproduction. 

If  the  control  of  the  dominant  over  the  subordinate  parts  in  the 
individual  is  accomplished  by  means  of  transmitted  impulses  or 
changes  which  show  a  decrement  with  transmission  and  a  limit  of 
effectiveness,  then  physiological  isolation  of  a  part  may  be  brought 
about  in  four  different  ways  (Child,  'iia).  First,  physiological 
isolation  may  result  from  increase  in  size  to  or  beyond  the  limit  of 
dominance.  Many  of  the  phenomena  of  budding,  fission,  etc.. 
which  occur  in  consequence  of  growth,  both  in  plants  and  in  animals. 
are  examples. 

Secondly,  physiological  isolation  may  result  from  a  decrease 
in  the  Umit  of  dominance,  which  in  turn  is  the  consequence  of  a 
decrease  in  rate  of  metabohsm  in  the  dominant  part.  It  is  a  well- 
known  fact  that  many  plants  give  rise  to  buds  or  other  reproductive 
bodies  under  conditions  unfavorable  to  metaboUc  activity,  and 
while  this  form  of  reproduction  has  often  been  regarded  teleo- 
logically  as  in  some  sense  an  attempt  of  the  plant  to  save  its  own 
life,  it  is  undoubtedly  to  be  interpreted  as  the  result  of  a  decrease 
in  the  hmit  of  dominance.  The  formation  of  new  buds  in  plants 
in  consequence  of  the  removal  or  inhibition  of  metabolism  of  the 
dominant  region,  the  vegetative  tip,  are  likewise  reprixluctive 
processes  which  belong  to  this  categor>\     In  the  lower  animals  also 


232  SENESCENCE  AND  REJUVENESCENCE 

many  cases  are  known  where  conditions  which  decrease  metabolism 
bring  about  budding  or  fission.  A  comparison  of  these  two  methods 
of  physiological  isolation  makes  it  evident  that  the  same  result, 
viz.,  the  physiological  isolation  of  parts  and  their  development  into 
new  individuals,  may  be  attained  by  subjecting  the  organism  to 
conditions  which  act  in  very  different  ways,  producing  in  the  one 
case  an  increase  in  rate  of  metaboHsm,  growth,  and  increase  in  size, 
in  the  other  a  decrease  in  rate  of  metabolism  (Child,  'lo).  It  is  pos- 
sible that  both  of  these  factors  are  concerned  in  many  cases  of  bud- 
ding and  fission,  that  is,  if  an  organism  has  attained  a  size  at  which 
some  part  is  approaching  physiological  isolation,  a  sHght  physiologi- 
cal depression  may  bring  about  a  sufficient  isolation  to  initiate 
dediiTerentiation  and  reproduction. 

Thirdly,  physiological  isolation  of  a  part  may  conceivably  result 
from  a  decrease  in  the  conductivity  of  the  path  over  which  the 
correlative  factors  from  the  dominant  region  are  transmitted. 
In  many  organisms  the  conductivity  of  the  paths  apparently 
increases  as  the  morphological  differentiation  of  conducting  struc- 
tures proceeds  during  development,  so  that  in  spite  of  a  decrease  in 
rate  of  general  metaboHsm  the  general  physiological  limits  of  the  indi- 
vidual are  extended  and  physiological  isolation  of  parts  is  delayed 
or  prevented.  In  many  of  the  flowering  plants,  for  example,  new 
growing  tips  arise  and  pass  through  the  early  stages  of  their  devel- 
opment at  very  short  distances  from  each  other  and  from  the  axial 
growing  tip  (Fig.  loi),  but  in  later  stages,  when  the  conducting 
structures  are  fully  developed,  the  dominance  of  the  growing  tip 
extends  over  a  much  greater  distance.  In  the  flatworms  likewise 
the  length  which  the  individual  attains  before  formation  of  a  new 
zooid  at  the  posterior  end  increases  up  to  a  certain  point  with 
advancing  development  (Child,  'iic),  while  any  considerable 
changes  in  conductivity  in  the  opposite  direction  may  bring  about 
reproduction  in  many  cases. 

And,  finally,  it  is  possible  that  physiological  isolation  of  a  part 
may  result  from  the  direct  action  of  external  factors  upon  it, 
increasing  its  rate  of  metaboHsm,  or  otherwise  altering  it,  so  that  it 
is  less  receptive,  or  no  longer  subordinate  to  the  correlative  factors, 
and  so  becomes  independent  in  spite  of  them.     In  various  plants 


INDIVIDUATION  AND  REPRODUCTION 


233 


the  development  of  buds  can  be  induced,  in  spite  of  the  presence  and 
activity  of  the  chief  growing  tip,  by  subjecting  the  part  concerned 
to  external  conditions  especially  favorable  for  growth  and  develop- 
ment. To  what  extent  this  process  of  physiological  isolation  occurs 
in  nature  is  as  yet  a  question,  though  it  probably  occurs  very  fre- 
quently. 

Many  cases  of  agamic  reproduction  have  not  as  yet  been  ana- 
lyzed from  this  point  of  view,  but  it  appears  probable  that  all  arc  the 
result  of  either  physiological 
or  physical  isolation.  In 
some  cases,  where  the  degree 
of  individuation  is  sHght, 
physical  isolation  is  probably 
the  primary  factor,  that  is, 
some  internal  or  external  con- 
dition operates  to  isolate  a 
part  physically  from  other 
parts  and  reproduction  re- 
sults. This  may  occur  in  va- 
rious cases  of  spore  formation 
among  the  lower  plants, 
although  even  here  it  is  prob- 
able that  physical  isolation  is 
possible  only  because  the 
parts  are  normally  but 
slightly  subordinated  to  a 
dominant  region. 

We  may  conclude,  then, 
that  the  first  step  in  agamic 
reproduction  is  the  isolation 

of  a  part  from  the  correlative  conditions  in  the  individual  which 
determine  its  existence  and  persistence  as  a  part.  In  at  least 
many  cases  this  isolation  is  primarily  physiological,  rather  than 
physical.  In  consequence  of  tliis  isolation  the  part  undergoes 
more  or  less  dedifferentiation,  a  new  individuation  arises  in  it 
in  various  ways,  some  of  which  have  been  analyzed  in  certain 
cases   (Child,    '14/^    '14^),   but   which   cannot  be  discussed   here. 


Fig.  ioi. — Longitudinal  section  of  the 
apical  region  of  a  seed  plant:  a,  growing  tip; 
b,  developing  leaves;  c,  a.\illar>'  buds.  From 
Strasburger,  etc.,  '08. 


234  SENESCENCE  AND  REJUVENESCENCE 

Such  reproduction  is  possible  only  where  the  isolated  part  is  capable 
of  reacting  to  the  isolation  by  dedifferentiation  and  reconstitution. 
According  to  this  conception,  agamic  reproduction  in  organisms 
results  in  one  way  or  another  from  the  physiological  or  physical  iso- 
lation of  a  subordinate  part  from  the  influence  of  the  dominant  part. 
At  first  glance  gametic  or  sexual  reproduction  appears  to  be  a  totally 
different  kind  of  reproduction,  but,  except  for  the  occurrence  of 
fertilization,  it  is  in  reality  very  similar  to  the  agamic  process. 
Before  taking  up  the  problem  of  sexual  reproduction,  however,  it  is 
necessary  to  consider  the  relation  between  individuation,  agamic 
reproduction,  and  the  age  cycle. 

REFERENCES 

BlEDERMANN,  W. 

1903.  "Elektrophysiologie,"  Ergebn.  d.  Physiol.,  Jhg.  II,  Abt.  II. 

BORUTTAU,  H. 

1901.  "Die  Aktionsstrome  und  die  Theorie  der  Nervenleitung,"  Arch, 
f.  d.  ges.  Physiol.,  LXXXIV. 

Bresslau,  E. 

1904.  "Beitrage  zur  Entwicklungsgeschichte  der  Turbellarien:  I,  Die 
Entwicklung  der  Rhabdocolen  und  AUoiocolen,"  Zeitschr.  f.  wiss. 
ZooL,  LXXVI. 

Child,  C.  M. 

1907a.  "An  Analysis  of  Form  Regulation  in  Tuhidaria:  I,  Stolon- 
Formation   and  Polarity,"  Arch.  J.  Entwickelungsmech.,  XXIII. 

19076.  "An  Analysis,  etc.:  IV,  Regional  and  Polar  Differences  in  the 
Time  of  Hydranth-Formation  as  a  Special  Case  of  Regulation  in 
a  Complex  System,"  Arch.  f.  Entwickelungsmech.,  XXIV. 

1907c.  "An  Analysis,  etc.:  V,  Regulation  in  Short  Pieces,"  Arch.  f. 
Entwickelungsmech . ,  XXIV. 

1910.  "Physiological  Isolation  of  Parts  and  Fission  in  Planaria,^'  Arch, 
f.  Entwickelungsmech.,  XXX  (Festband  f.  Roux),  II.  Teil. 

191 10.  "Die  physiologische  Isolation  von  Teilen  des  Organismus,"  Vortr. 
und  Aufs.  a.  Entwickelungsmech.,  XI. 

191 16.  "Studies  on  the  Dynamics  of  Morphogenesis  and  Inheritance  in 
Experimental  Reproduction:  II,  Physiological  Dominance  of 
Anterior  over  Posterior  Regions  in  the  Regulation  of  Planaria 
dorotocephala,"  Jour,  of  E.xp.  ZooL,  XL 

191  ic.  "Studies,  etc.:  Ill,  The  Formation  of  New  Zooids  in  Planaria 
and  Other  Forms,"  Jour,  of  Exp.  ZooL,  XI. 


INDIVIDUATION  AND  REPRODUCTKJX  235 

Child,  C.  M. 

191 2.  "Studies,  etc.:  IV,  Certain  Dynamic  Factors  in  the  Regulation 
of  Planaria  dorotoccphala  in  Relation  to  the  Axial  Gradient," 
Jour,  of  Exp.  Zool.,  XIII. 

1913a.  "Certain  Dynamic  Factors  in  Experimental  Reproduction  and 
Their  Significance  for  the  Problems  of  Reproduction  and  Develop- 
ment," Arch.  f.  Entwickelungsmech.,  XXXV. 

19136.  "Studies,  etc.:  VI,  The  Nature  of  the  Axial  Gradients  in  Planaria 
and  Their  Relation  to  Antero-posterior  Dominance,  Polarity  and 
Symmetry,"  Arch.  f.  Entwickelungsmech.,  XXXVII. 

1914a.  "Susceptibility  Gradients  in  Animals,"  Science,  XXXIX. 

19146.  "Studies,  etc.:  VII,  The  Stimulation  of  Pieces  by  Section  in 
Planaria  doroiocephala,"  Jour,  of  Exp.  Zool.,  X\T. 

1914c.  "Studies,  etc.:  VIII,  Dynamic  Factors  in  Head-Determination 
in  Planaria,''''  Jour,  of  Exp.  Zool.,  XVII. 

DUCCESCHI,  V. 

1901.  "tJber  die  Wirkung  engbegrenzter  Nervencompression,"  Arch.  f. 
d.  ges.  Physiol.,  LXXXIII. 

Fischer,  A. 

191 1.  "Ein  Beitrag  zur  Kenntnis  des  Ablaufes  des  Erregungsvorgangs 
im  marklosen  Warmbluternerven,"  Zeitschr.  f.  Biol.,  LVI. 

Fitting,  H. 

1907.  "Die  Reizleitungsvorgange  bei  den  Pflanzen,"  Sonderabdr.  aus 
Ergehn.  d.  Physiol.,  Jhg.  IV  u.  \'.     Wiesbaden. 

KOWALEWSKY,  A. 

1871.  "  Embryologische  Studien  an  Wiirmern  und  Arlhropoden,"  Mint. 
Acad.  St.  Petcrshourg,  (7)  XVI. 

Kretzschmar,  p. 

1904.  "iJber  Entstehung  und  Ausbreitung  der  Plasmastromung  in  Folge 
von  Wundreiz,"  Jahrbiicher  f.  wiss.  Bot.,  XXXIX. 

LODHOLZ,  E. 

1913.  "Das  Dekrement  der  Erregungswelle  im  erstickenden  Ncr\'cn," 
Zeitschr.  f.  allgem.  Physiol.,  XV. 

]\IcCallum,  W.  B. 

1905.  "Regeneration  in  Plants,"  Bot.  Gazette,  XL. 

Morgan,  T.  H. 

1904.  "Regeneration  of  Heteromorphic  Tails  in  Posterior  Pieces  of 
Planaria  simplicissima,"  Jour,  of  Exp.  Zool.,  I. 

Patterson,  J.  T. 

1913.  "  Polyembryonic  Development  in  Tatusia  novcntcincta,"  Jour. 
of  Morphol.,  XXIV. 


236  SENESCENCE  AND  REJUVENESCENCE 

Seubert,  M. 

1866.     Lehrhuch  der  gesammten  Pflanzenkunde.     IV.  Auflage. 

Sherrington,  C.  S. 

1906.     The  Integrative  Action  of  the  Nervous  System.     New  York. 
Strasburger,  E.,  Noll,  F.,  Schenck,  H.,  und  Karsten,  G. 

1908.     Lehrhuch  der  Botanik.     IX.  Auflage.     Jena. 

Tashiro,  S. 

1913a.  "Carbon  Dioxide  Production  from  Nerve  Fibers  When  Resting 

and  When  Stimulated;   a  Contribution  to  the  Chemical  Basis  of 

Irritability,"  Am.  Jour,  of  Physiol.,  XXXII. 
19136.  "A  New  Method  and  Apparatus  for  the  Estimation  of  Exceedingly 

Minute  Quantities  of  Carbon  Dioxide,"  Am.  Jour,  of  Physiol., 

XXXII. 

Verworn,  M. 

1913.     Irritability.     New  Haven,  Conn. 

Wilson,  H.  V. 

1889.     "The  Embryology  of  the  Sea  Bass,"  Bull,  of  the  U.S.  Fish  Com- 
mission, IX. 


CHAPTER  X 
THE  AGE  CYCLE  IN  PLANTS  AND  THE  LOWER  AXBLXLS 

Any  consideration  of  the  age  cycle  and  particularly  of  rejuve- 
nescence in  plants  would  be  incomplete  without  reference  to  a 
remarkable  book,  Considerations  on  the  Phenomenon  of  Rejuvenescence 
in  Nature,^  by  the  German  botanist  Alexander  Braun,  published  in 
185 1.  The  book  is  remarkable,  not  only  as  a  consideration  of  re- 
juvenescence, but  as  one  of  the  pre-Darwinian  statements  of  a 
theory  of  evolution.  This  work  became  known  to  me  only  after 
I  had  attained  dehnite  conclusions  on  the  basis  of  experiment,  and 
it  has  been  a  matter  of  very  great  interest  to  discover  to  how  great 
an  extent  Braun  had  anticipated  in  his  views  the  results  of  experi- 
ment. He  regards  reproduction  in  the  broadest  sense  and  pri- 
marily cell  reproduction  as  the  basis  of  rejuvenescence,  describes 
and  discusses  dedifferentiation,  and  recognizes  clearly  the  important 
fact  that  the  vegetative  Ufe  of  plants  is  in  most  cases  a  series  of 
reproductions.  In  fact,  the  conclusions  reached  in  the  present 
chapter  are  in  many  respects  essentially  those  of  Braun.  but  modi- 
fied and  brought  into  relation  with  modern  physiological  conceptions 
and  with  my  own  experimental  results  on  the  lower  animals. 

INDIVIDUATION  AND  AGAMIC  REPRODUCTION  IN  THE 
LIFE  CYCLE  OF  PLANTS 

According  to  the  conception  of  individuation  discussed  in  the 
preceding  chapter,  every  growing  tip,  together  with  the  region 
which  it  dominates,  is  in  greater  or  less  degree  a  plant  individual. 
All  except  the  simplest  plants  therefore  are  in  reality,  as  botanists 
have  repeatedly  pointed  out,  asexual  colonies  consisting  of  a  larger 
or  smaller  number  of  individuals  which  are  not  completely  isolated 
from  each  other.  In  animal  colonies  such  individuals  are  commonly 
known  as  zooids,  and  for  convenience  the  individuals  in  a  plant 
colony  may  be  termed  phytoids.  In  most  plants  there  is  evidently 
also  some  degree  of  individuation  of  the  colony  as  a  whole,  for  new 

^Bdrachtungen  iibcr  die  Erscheimmg  der  Verjiingung  in  dcr  Natur. 

237 


238  SENESCENCE  AND  REJUVENESCENCE 

buds  arise  in  a  definite  sequence  and  space  relation  to  each  other, 
and  numerous  experiments  have  demonstrated  that  the  growing  tip 
of  the  main  axis  which  is  often  itself  a  complex  of  young  buds 
dominates  to  a  greater  or  less  extent  the  whole  stem.  In  the  root 
system  somewhat  similar  relations  exist  between  the  growing  region 
of  the  main  axis  and  the  lateral  branches.  In  such  plants  also 
the  relation  between  the  spatial  boundaries  of  the  individual  and 
the  development  of  conducting  paths  is  clearly  apparent.  Various 
facts  indicate  that  in  vascular  plants  transmission  of  stimuli  takes 
place  more  rapidly  and  to  greater  distances  along  the  vascular 
bundles  than  through  other  tissues  (see  Fitting,  '07),  and  some 
botanists  have  regarded  the  sieve  vessels  as  the  chief  conducting 
elements.  In  the  apical  growing  region  of  the  main  axis,  where  the 
tissues  are  embryonic  and  vascular  bundles  have  not  yet  developed, 
new  buds,  i.e.,  new  phytoids,  often  arise  at  very  short  distances  from 
each  other  in  spite  of  the  high  rate  of  metabolism  in  this  region,  while 
farther  down  the  stem,  where  the  vascular  bundles  have  differen- 
tiated, the  dominance  of  a  growing  tip  may  extend  over  much  greater 
distances  and  the  dominance  of  the  whole  growing  region  at  the 
apical  end  of  the  main  axis  may  extend  over  the  whole  length  of 
the  stem. 

The  prothallia  of  the  liverworts  and  ferns  apparently  are  single 
plant  individuals,  at  least  during  their  earlier  stages,  and  some 
throughout  hfe,  with  a  dominant  growing  region  possessing  the 
highest  rate  of  metabolism  and  a  metabolic  gradient  along  the 
axis.  But  even  these  prothallia  in  many  cases  show  agamic 
reproduction  after  a  certain  stage  is  reached  or  under  certain 
conditions. 

Many  botanists  regard  the  formation  of  new  growing  tips  in  the 
vegetative  life  of  the  plant  merely  as  growth,  and  reserve  the 
term  "reproduction"  for  the  specialized  forms  of  reproduction, 
such  as  the  formation  of  spores,  gemmae,  and  other  reproductive 
bodies,  including  the  gametes.  Actually,  however,  each  new 
growing  tip  represents  a  new  individuation  with  the  potentiahties 
of  a  whole  plant  and  fails  to  produce  a  whole  plant  only  because 
it  is  organically  connected  with  other  parts.  Properly  speaking, 
then,  the  formation  of  new  growing  tips  or  buds  is  a  reproductive 


AGE  CYCLE  IX  PLANTS  AND  LOWER  ANIMALS  239 

process  as  truly  as  any  other  more  specialized  kinds  of  reproduction. 
For  convenience  it  may  be  distinguished  from  these  as  vegetative 
reproduction. 

Agamic  reproduction  is,  then,  a  characteristic  feature  of  the 
vegetative  hfe  of  plants.  The  degree  of  individuation  is  so  low  that 
growth  leads  very  readily  to  physiological  isolation  of  parts  and 
new  individuation,  and,  without  doubt,  also,  conditions  which 
decrease  the  metaboHc  activity  of  the  dominant  region  accomplish 
the  same  result.  Most  of  what  is  commonly  called  growth  in  plants 
involves  the  formation  of  new  phytoids.  The  new  buds  of  each 
season  or  active  period  in  perennial  plants  are  new  individuals. 

THE   VEGETATIVE    LIFE    OF   PLANTS   IX   RELATION   TO    SENESCENCE 

It  is  important  at  the  outset  to  distinguish  clearly  between  the 
occurrence  of  senescence  in  the  plant  as  a  whole  and  its  occurrence 
in  single  phytoids  or  parts.  The  vegetative  propagation  of  plants 
from  cuttings,  which  in  the  case  of  some  species — such,  for  example, 
as  the  banana — -has  continued  for  hundreds  of  years,  and  the 
capacity  of  the  lower  plants  for  indefinite  vegetative  growth  under 
proper  nutritive  conditions  demonstrate  clearly  enough  that  the 
life  of  the  plant  or  some  part  of  it  may  continue  indefinitely  without 
any  indication  of  aging.  On  the  other  hand,  in  many  plants  the 
length  of  life  under  natural  conditions  is  more  or  less  definitely 
limited,  though  the  life  period  may  range  from  a  few  hours  to 
centuries  in  dift'erent  forms.  In  the  higher  plants,  particularly 
in  the  woody  forms,  certain  of  the  cells  cease  sooner  or  later  to 
divide,  undergo  specialization,  show  all  signs  of  aging,  and  sooner 
or  later  die,  while  others  apparently  remain  young  indcfiniteK'. 
Must  we  then  conclude  that  some  plants  and  not  others  undergo 
senescence?  In  all  except  the  earlier  stages  of  the  life  cycle  the 
old  differentiated  or  dead  cells  usually  constitute  by  far  the  larger 
proportion  of  the  plant  mass,  the  young  cells  in  which  growth  and 
division  occur  being  often  but  a  minute  fraction  of  the  whole.  Are 
we  then  to  conclude  that  some  plants  and  not  others,  and  some  parts 
of  a  plant  and  not  others,  undergo  senescence  and  die  of  old  age  ? 

As  regards  metabolic  condition,  it  is  well  known  that  plants 
and  plant  organs  in  general  show  a  higher  rate  of  oxidation  in 


240  SENESCENCE  AND  REJUVENESCENCE 

earlier  stages  of  development,  when  they  are  physiologically 
young,  than  in  later  stages.  Under  given  external  conditions 
the  rate  of  oxidation  in  buds,  for  example,  is  higher  than  in 
fully  developed  stems  and  leaves,  and  in  germinating  seeds  it  is 
higher  than  in  later  stages  of  development.  Evidently  in  plants, 
as  in  animals,  a  decrease  in  rate  of  oxidation,  a  real  metabolic 
senescence,  occurs  and  is  accompanied  by  a  decreasing  rate  of 
growth  and  by  progressive  differentiation  to  a  greater  or  less  ex- 
tent.' The  case  of  the  flower,  which  shows  a  very  high  rate  of 
respiration  is  considered  in  chap.  xiv. 

The  metabolic  changes  of  age  proceed  much  more  rapidly  in 
some  parts  of  the  plant  than  in  others.  The  leaf  and  the  stem 
undergo  differentiation  and  grow  old,  at  least  in  large  part,  while 
the  growing  tip  and  other  meristematic  tissues  seem  to  remain 
young  indefinitely  or  to  undergo  senescence  relatively  slowly. 

There  can  be  no  doubt  that  the  behavior  of  the  plant  and  its 
parts  in  relation  to  senescence  depends  upon  the  relation  between 
individuation  and  reproduction.  In  general,  the  higher  the  degree 
of  individuation,  or  of  physiological  integration,  the  more  definite 
and  continuous  the  process  of  senescence,  because  reproduction 
is  less  frequent.  In  Part  II  it  was  shown  for  various  animal  species 
that  the  reconstitution  of  a  new  individual  from  a  part  of  a  pre- 
existing individual  is  associated  with  some  degree  of  rejuvenescence. 
In  the  case  of  the  plant  similar  changes  undoubtedly  occur  when  the 
part  concerned  in  the  reconstitution  is  a  differentiated  part,  as  it 
often  is,  but  the  cells  chiefly  concerned  in  reproduction  in  the  higher 
plants  are  commonly  regarded  as  undifferentiated  or  embryonic, 
i.e.,  as  physiologically  young.  In  general  the  degree  of  rejuvenes- 
cence associated  with  the  reconstitution  of  a  part  into  a  new  whole 
depends  upon  the  degree  of  individuation.  In  certain  of  the  algae 
and  fungi  the  degree  of  individuation  is  so  slight  it  is  diflicult  to 
determine  whether  the  plant  is  anything  more  than  a  cell  or  an 
aggregate  of  cells.  In  such  plants  as  these  the  formation  of  a  new 
individual  from  any  part  of  the  old  doubtless  involves  Httle 
change  beyond  nuclear  or  cell  division,  and  therefore   but   httle 

'For  references  to  literature  concerning  respiration  in  plants  see  Pfeffer,  '97, 
pp.  523-31;  Nicolas,  '09.     See  also  Nicolas,  '10. 


AGE  CYCLE  IN  PLANTS  AND  LOWER  AXLMALS  241 

dedifferentiation  and  rejuvenescence  occur.  In  such  cases,  however, 
the  slight  degree  of  individuation  determines  that  reproduction  shall 
be  almost  continuous  during  vegetative  existence;  consequently 
there  is  but  little  possibility  of  differentiation  and  senescence. 
Under  such  conditions  the  plant  as  a  whole  may  remain  physiologi- 
cally young  for  an  indefinite  period,  simply  because  new  individ- 
uations from  parts  of  pre-existing  individuals  occur  ver>'  frequently. 
Even  in  those  algae  and  fungi  which  consist  of  a  single  multinucleate 
cell,  the  localization  and  development  of  a  new  branch  unquestion- 
ably brings  about  some  degree  of  reconstitutional  change,  for  it 
involves  a  local  increase  in  the  rate  of  growth.  It  is  the  continued 
reorganization  which  keeps  such  plants  from  growing  old  under 
such  conditions. 

In  some  of  these  lower  plants  certain  parts,  usually  those  which 
bear  the  spores,  become  more  highly  individuated  than  the  rest  of 
the  plant  and  consequently  undergo  a  greater  degree  of  differen- 
tiation and  usually  undergo  a  more  or  less  continuous  senescence 
and  die  of  old  age,  while  the  less  highly  individuated  and  so  less 
differentiated  portions  may  continue  to  live  and  remain  voung 
indefinitely.  Many  of  the  fungi,  and  particularly  the  mushrooms 
and  related  forms,  are  cases  in  point.  The  mushroom  itself  is  the 
more  highly  individuated  spore-bearing  portion  of  a  plant  whose 
vegetative  form  consists  of  thread-like  branching  hyphae.  which 
are  merely  strings  of  like  cells  attached  end  to  end.  The  mush- 
room passes  through  a  definite  course  of  development  and  differ- 
entiation, attains  maturity,  ceases  to  grow,  and  finally  dies, 
but  the  vegetative  hyphae  may  continue  to  grow  indefinitely 
without  any  perceptible  progressive  morphological  or  physiological 
change. 

The  course  of  plant  evolution  from  the  lower  to  the  higher  forms 
is  characterized  by  an  increasing  differentiation  in  the  vegetative 
plant  body  and  a  more  and  more  definite  limitation  of  vegetative 
reproduction,  at  least  under  the  usual  conditions,  to  certain  parts 
or  tissues  of  the  plant  which  remain  unditYerentiated  and  physio- 
logically young  for  a  long  time  or  indefinitely,  while  the  other  parts 
undergo  differentiation,  senescence,  and.  it  may  be,  death.  In 
the  mosses  and  ferns  the  regions  which  retain   tluir  youth  and 


242  SENESCENCE  AND  REJUVENESCENCE 

embryonic  character  are  more  or  less  definitely  localized  as  vege- 
tative tips  and  certain  other  regions,  but  in  these  forms  vegetative 
reproduction  often  occurs  from  other  more  highly  differentiated 
parts  of  the  plant  as  well  as  from  these  regions.  In  the  seed  plants, 
however,  these  embryonic  or  meristematic  tissues,  as  they  are 
called,  are  still  more  definitely  locaHzed,  and  in  the  highest  forms 
other  regions  of  the  plant  body  usually  take  but  httle  part  in 
vegetative  reproduction,  at  least  as  long  as  the  meristematic 
tissues  are  present  and  active. 

The  continued  existence  of  this  embryonic  tissue  in  plants  at 
the  same  time  that  differentiation  and  senescence  are  occurring  in 
other  parts  raises  at  once  the  question  why  different  parts  of  the 
plant  behave  differently  in  these  respects.  While  it  is  impossible 
to  give  a  complete  answer  to  this  question,  certain  facts  indicate 
very  clearly  the  direction  in  which  an  answer  is  to  be  sought. 

In  the  first  place,  cell  division  in  the  plant  occurs  chiefly  in  the 
embryonic  cells  and  the  earlier  generations  of  their  descendants. 
The  susceptibihty  experiments  on  the  infusoria  recorded  in  Part  II 
(pp.  141-42)  indicate  that  in  those  forms  cell  division  is  accompa- 
nied by  some  degree  of  rejuvenescence  and  in  all  cases  cell  division 
is  a  reproductive  process,  and  as  such  involves  more  or  less  rejuve- 
nescence. Cells  which  divide  rapidly  do  not  undergo  any  great 
degree  of  differentiation,  and  cells  which  resume  division  after 
udergoing  differentiation  first  undergo  a  greater  or  less  degree  of 
dedifferentiation.  In  short,  continued  nuclear  and  cell  division 
is  undoubtedly  an  important  factor  in  maintaining  cells  in  the 
embryonic  condition  and  continued  metabohsm  in  the  presence  of 
nutrition  and  without  cell  division  is  a  factor  in  senescence.  But 
cell  division  alone  is  by  no  means  always  adequate  to  maintain  cells 
in  the  embryonic  condition.  In  embryonic  development  many 
cells  apparently  grow  old  in  spite  of  division,  and  sooner  or  later 
division  becomes  impossible  or  possible  only  under  altered  condi- 
tions. 

If  frequent  cell  division  is  a  factor  in  maintaining  certain  plant 
tissues  in  the  embryonic  condition,  we  must  inquire  why  cell 
division  is  more  frequent  in  certain  regions  than  in  others.  This 
question  we  are  unable  to  answer  at  present,  since  our  knowledge 


AGE  CYCLE  IN  PLANTS  AND  LOWER  ANIMALS  243 

of  the  conditions  determining  cell  division  and  of  the  comiitions 
in  different  parts  of  the  plant  is  very  incomplete.  As  regards  the 
plant,  we  can  only  say  that  in  certain  regions  progressive  and 
regressive  changes  balance  each  other  more  or  less  completely, 
and  consequently  these  regions  remain  undifferentiated  and  voung 
or  undergo  differentiation  and  senescence  very  slowly,  while  in 
other  regions  progressive  changes  are  more  nearly  or  quite  con- 
tinuous. The  fact  that  differentiated  cells  may  become  embr\onic 
or  embryonic  cells  may  differentiate  when  physiological  conditions 
change,  shows  that  these  differences  in  behavior  depend,  not  upon 
a  fundamental  difference  in  constitution  of  the  cells,  but  upon  the 
conditions  to  which  they  are  subjected  in  the  regions  of  the  plant. 
The  solution  of  the  problem  undoubtedly  lies  in  the  physiological 
make-up  of  the  plant  individual  as  a  whole  and  the  character  of 
its  metabolism. 

But  even  in  the  so-called  embryonic  tissue  of  the  higher  plants 
the  cells  are  not  absolutely  alike.  Some  degree  of  individuation 
exists,  for  the  activities  of  this  tissue  are  orderly,  and  a  relation 
of  dominance  and  subordination  exists  in  it.  Many  facts  indicate 
the  existence  of  an  axial  gradient  in  rate  of  metabolism,  the  region 
of  the  vegetative  tip  possessing  the  highest  rate  and  dominating 
other  parts.  Since  this  is  the  case,  the  formation  of  new  vegetative 
tips,  i.e.,  of  buds — a  characteristic  feature  of  the  vegetative  life 
of  most  of  the  higher  plants — must  involve  a  change  of  some  degree 
and  kind  in  the  embryonic  tissue.  This  change  is  probably  pri- 
marily an  increase  in  rate  of  metabolism  in  the  part  concerned,  but 
such  an  increase  in  rate  is  essentially  a  rejuvenescence  in  some 
degree.  The  changes  involved  in  these  vegetative  reproductions 
are  undoubtedly  slight  in  many  cases,  but  nevertheless  they 
constitute  a  factor  in  the  maintenance  of  the  embryonic  condition. 
Each  new  bud  formed  from  a  part  of  a  pre-existing  plant  individual 
involves  to  some  extent  a  reconstitutional  process,  even  though  it 
may  be  merely  an  increase  in  rate  and  the  establishment  of  a  new 
axial  gradient.  Vegetative  reproduction  is  then  another  factor 
concerned  in  retarding  the  progressive  course  of  senescence  and 
differentiation  in  the  plant  tissues  chiefly  concerned.  Observation 
confirms  this  conclusion,  for  we  find  that  the  plants  or  the  phytoids 


244  SENESCENCE  AND  REJUVENESCENCE 

of  a  plant  which  show  a  low  degree  of  individuation,  and  conse- 
quently frequent  vegetative  reproduction,  are  capable  of  continu- 
ing their  vegetative  activity  for  a  long  time  or  even  indefinitely, 
without  indications  of  senescence  of  the  meristematic  tissues,  while 
the  length  of  life  is  usually  more  or  less  definitely  Umited  in  plants 
or  phytoids  with  infrequent  or  no  vegetative  reproduction.  In 
various  plants  with  subterranean  stems,  such  as  the  flags  and 
rushes,  for  example,  the  stem  shows  repeated  vegetative  reproduc- 
tion, giving  rise  to  the  aerial  shoots,  and  its  length  of  hfe  is  appar- 
ently unhmited.  The  aerial  shoots,  however,  show  a  much  higher 
degree  of  individuation  with  Kttle  or  no  vegetative  reproduction, 
and  their  length  of  life  is  short. 

In  spite  of  the  occurrence  of  nuclear  and  cell  division  and 
vegetative  reproduction,  however,  the  vegetative  tips  and  other 
meristematic  tissues  of  many  plants  show  indications  of  progres- 
sive changes.  The  shoots  produced  from  later  buds  may  differ 
in  character  from  those  of  earlier  origin,  the  later  leaves  often  differ 
in  form  and  structure  from  the  earher  and  the  rate  of  growth  may 
decrease  until  growth  finally  ceases  (Diels,  '06;  H.  M.  Benedict, 
'12,  '15).  The  relations  between  vegetative  growth  and  reproduction 
and  the  formation  of  tubers,  bulbs,  bulbiUi,  and  other  individuals  or 
parts  which  contain  nutritive  reserves  also  indicate  the  occurrence 
of  progressive  changes,  of  a  real  life  history,  although  Vochting 
('87,  '00)  and  others  have  shown  that  the  formation  of  reserve- 
bearing  structures,  like  other  features  of  the  Hfe  history,  can  be 
controlled  experimentally  by  retarding  or  accelerating  the  pro- 
gressive development  of  the  plant  with  the  aid  of  external  con- 
ditions. There  is  much  evidence  in  favor  of  the  view  that  the 
change  from  vegetative  reproduction  to  flowering  is  connected  with 
advancing  senescence  and  specialization  of  the  meristematic  tissues 
of  the  plant  (see  chap.  xiv). 

The  conclusion  to  which  the  various  lines  of  evidence  point  is 
that  senescence  is  a  characteristic  feature  of  the  vegetative  life  of 
plants,  but  that  it  is  not  an  uninterrupted,  continuous  process. 
The  low  degree  of  individuation  in  plants  determines  a  high  fre- 
quency of  agamic  reproduction,  which  brings  about  a  greater  or  less 
degree  of  rejuvenescence  and  so  balances  more  or  less  completely 


AGE  CYCLE  IN  PLANTS  AND  LOWER  ANIMALS  245 

the  progressive  changes.  Undoubtedly  also  the  character  of 
metabolism  determines  a  more  rapid  senescence  with  less 
capacity  for  regression  in  some  plants  than  in  others,  and  the 
work  of  Klebs  and  many  other  investigators  on  the  effect  of 
nutritive  and  other  external  conditions  indicates  that  these 
also  influence  the  rate  of  senescence  and  the  character  of 
differentiation. 

The  process  of  differentiation  of  the  plant  cell  is  apparently  not 
fundamentally  different  from  that  of  the  animal  cell.  It  consists 
in  the  development  of  relatively  stable  structural  features,  the  depo- 
sition of  relatively  inactive  substances  in  the  cytoplasm  or  on  its 
surface,  in  many  cases  substances,  such  as  starch,  w^hich  may  serve 
as  nutrition  under  other  conditions.  The  accumulation  of  fluid  in 
vacuoles  is  also  a  very  characteristic  feature  of  differentiation  in 
plant  cells.  In  general  here,  as  in  animals,  the  process  of  differen- 
tiation involves  a  decrease  in  the  proportion  of  the  chemically 
active  "undifferentiated"  protoplasm. 

THE  OCCURRENCE  OF  DEDIFFERENTIATION  AND  REJUVENESCENCE 

IN  PLANT   CELLS 

It  was  pointed  out  above  that  the  formation  of  a  new  vegeta- 
tive tip  by  the  embryonic  tissue  of  the  plant  must  involve  a  new 
individuation  and  some  slight  degree  of  physiological  rejuvenes- 
cence. But  the  occurrence  of  dedifferentiation,  even  among  the 
higher  plants,  is  not  limited  to  such  changes  as  this.  Cells  which 
have  clearly  lost  their  embry6nic  character  and  have  undergone 
more  or  less  morphological  as  well  as  physiological  change  have 
been  repeatedly  observed  to  undergo  dedifferentiation  and  become 
embryonic,  both  in  appearance  and  in  behavior.  E.xperiment  has 
demonstrated  again  and  again  that  among  the  lower  plants  every 
cell,  or  almost  every  cell,  of  the  plant  body  may  be  capable  of  giving 
rise  to  a  new  individual  with  all  the  capacities  of  the  individual 
which  develops  from  the  egg.  Among  the  liverworts  and  in  many 
of  the  ferns  the  cells  of  the  prothallium  very  generally  retain  the 
capacity  to  give  rise  to  new  individuals,  either  when  physically 
isolated  by  section,  or  when  physiologically  isolated  by  growth  of 
the  prothallium,  removal  of  the  growing  tip.  or  other  conditions, 


246  SENESCENCE  AND  REJUVENESCENCE 

and  this  change  in  behavior  in  all  cases  undoubtedly  involves  a 
greater  or  less  degree  of  rejuvenescence. 

Even  in  the  seed  plants  new  growing  tips  which  are  capable  of 
developing  into  new,  complete  plants  and  producing  sex  cells  often 
arise  from  cells  which  have  undergone  visible  differentiation.  In 
Begonia,  for  example,  the  formation  of  so-called  adventitious  buds 
from  epithehal  cells  of  the  leaf  has  been  observed,  and  in  many 
other  plants  new  individuals  develop  from  cells  which  are  far  from 
being  embryonic.  The  cells  concerned  in  such  cases  lose  their 
differentiated  character  and  return  to  the  embryonic  condition, 
resume  growth  and  division,  and  enter  upon  a  new  developmental 
cycle.  The  formation  of  meristematic,  or  embryonic,  tissue  from 
the  parenchyma  of  the  leaf  petiole  and  from  other  differentiated 
tissues  has  also  often  been  noted.  The  transformation  of  inflores- 
cence into  vegetative  shoots  has  been  experimentally  induced  by 
Klebs  and  others  in  various  plants,  and  its  occurrence  in  nature 
has  been  repeatedly  observed.  One  case  described  by  Winkler 
('02)  in  a  species  of  Chrysanthemum  deserves  brief  mention.  In  the 
disk  flowers  the  style  formed  the  stem  and  the  stigma  gave  rise 
to  two  leaves  like  normal  upper  leaves  of  the  species.  The 
embryo  sac  developed  and  the  pollen  was  capable  of  germination, 
but  the  embryo  died  at  an  early  stage.  The  corolla  became  green, 
the  vascular  system  increased  and  branched,  and  stomata  appeared. 
In  this  case  the  flower  evidently  underwent  a  partial  transformation 
into  a  vegetative  structure,  and  this  change  must  have  involved 
some  considerable  degree  of  dedifferentiation  and  rejuvenescence. 

In  fact,  the  occurrence  of  dedifferentiation  among  plants  has 
been  demonstrated  beyond  question.'  Certainly  in  the  plant,  as 
in  the  animal,  senescence  is  associated  with  specialization  and 
differentiation  of  cells,  and  it  is  just  as  certain  that  dedifferentiation 
is  accompanied  by  rejuvenescence.  Moreover,  the  increased  activ- 
ity in  growth  and  division  of  the  cells  concerned,  as  well  as  their 

'  The  following  references  will  serve  as  an  introduction  to  the  extensive  bibli- 
ography of  the  subject:  Brefeld,  '76,  '77;  Bums  and  Heddon,  '06;  von  Faber,  '08; 
Goebel,  '08,  pp.  141-65;  Heim,  '96;  Hildebrand,  '10;  Jost,  '08,  Vorlesung  26;  Klebs, 
'03,  '06a,  'obb;  Kohler,  '07;  Kreh,  'eg;  Magnus,  '06;  Miehe,  '05;  Noll,  '03;  Regel, 
'76;  Riehm,  '05;  Schostakewitsch,  '94;  Tobler,  '02,  '04;  Vochting,  '85;  Winkler, 
'02,  '07. 


AGE  CYCLE  IN  PLANTS  AND  LOWER  AXLMALS  247 

ability  to  go  through  a  new  course  of  development  and  differentia- 
tion, indicates  very  clearly  that  they  have  become  physiologically 
younger,  and,  though  I  know  of  no  observations  bearing  directly 
upon  this  point,  no  one  can  doubt  that  when  a  differentiated  cell 
dedift'erentiates  into  a  growing  tip  an  increase  in  rate  of  respiration 
and  other  metabolic  processes  occurs. 

THE  RELATION  OF  THE  DIFFERENT  FORMS  OF  AGAMIC  REPRODUCTION 

IN  PLANTS  TO  THE  AGE  CYCLE 

Most  plants  exhibit  more  than  one  form  of  agamic  reproduction, 
and  in  some  species,  e.g.,  certain  mosses,  several  dift'erent  forms 
occur.  But  two  forms  of  agamic  reproduction  are  particularly 
characteristic  of  nearly  all  plant  species,  one  the  vegetative  form 
of  reproduction,  often  called  vegetative  growth,  in  which  new  vege- 
tative individuals  essentially  similar  to  the  old  arise  by  the  forma- 
tion of  buds,  branches,  etc. ;  the  other  the  process  of  spore  formation, 
which  usually  occurs  only  in  certain  regions  of  the  plant  body  and 
after  a  period  of  vegetative  growth.  In  some  cases,  as  in  the  rusts, 
four  or  five  different  kinds  of  spores  are  produced  by  a  single  species. 
The  spore  is  in  general  a  cell  which  becomes  isolated  from  the 
plant  body  and  sooner  or  later  gives  rise  to  a  new  individual.  In 
some  cases  this  isolation  is  physiological,  in  others  it  is  physical. 
In  the  algae  and  fungi,  which  must  be  considered  before  turning  to 
the  higher  plants,  the  spores  usually  develop  into  individuals  like 
those  from  which  they  arose,  and  the  spore  may  be  either  a  resting 
or  a  motile  stage  between  two  vegetative  generations.  Spore  for- 
mation in  these  plants  is  essentially  a  process  of  complete  or  partial 
disintegration  of  existing  individuals  into  cells,  rather  than  the 
addition  of  new  individuals  as  the  result  of  growth,  as  in  vegetative 
reproduction  under  the  usual  conditions.  In  the  alga  Ulollin'x,  for 
example,  any  cell  of  the  filamentous,  unbranchcd  plant  body  may 
break  up  into  zoospores  (Figs.  102,  103);  in  the  branching  form 
Vaucheria  the  terminal  region  of  the  branch  separates  as  a  multi- 
nucleate zoospore  (Fig.  104).  Among  the  brown  algae  the  spores 
arise  by  separation  into  single  small  cells  of  the  contents  of  special 
organs,  the  sporangia  (Fig.  105).  In  the  fungus  Saprolcguia  (Fig. 
106)  the  sporangium  is  the  terminal  region  of  the  vegetative  Ixxly. 


248 


SENESCENCE  AND  REJUVENESCENCE 


while  in  Mucor  (Fig.  107,  A-C)  the  sporangium  arises  at  the  end  of 
a  specialized  stalk,  the  sporophore,  which  grows  out  of  the  nutri- 
tive substratum  into  the  air,  and  in  Penicillium  still  another  type  of 
sporophore  appears  (Fig.  108).  In  other  forms  still  other  methods 
of  spore  formation  occur  with  various  degrees  of  specialization  in 
the  spore-forming  organs,  but  everywhere  the  process  consists  in  a 


Figs.  102-105. — Formation  of  spores  in  various  algae:  Figs.  102,  103,  Ulothrix; 
Fig.  104,  a  stage  in  the  development  of  the  zoospore  in  Vaiicheria;  Fig.  105,  a  filament 
of  Ectocarpus  bearing  a  sporangium  and  at  the  left  a  more  highly  magnified  zoospore. 
From  Coulter,  etc.,  '10. 

disintegration  of  the  plant  body  or  some  part  of  it  into  independent 
cells. 

According  to  the  conception  of  individuation  presented  in  the 
preceding  chapter,  return  to  the  condition  of  the  free-living,  inde- 
pendent cell  must  mean  a  decrease  in  the  physiological  coherence  of 
the  plant  individual,  and  it  might  be  expected  to  result  from  con- 
ditions which  decrease  the  metabolism  of  the  plant  and  so  allow  it, 
or  a  part  of  it,  to  separate  into  its  constituent  units,  the  cell  indi- 


AGE  CYCLE  IN  PLANTS  AXD  LOWER  AMMALS 


249 


viduals.  Various  investigators,  prominent  among  whom  is  Klebs,' 
have  investigated  and  analyzed  the  external  conditions  which 
determine  spore  formation  in  the  algae  and  fungi,  and  the  results  of 
their  work  agree  well  with  this  idea. 


PI 

'^    "1.-'.   ■:. 

mm 

hi-,  m 


10? 


A 


;^;..;v/i.;.;.: 

■'■'C  ■  '^-' 

^;        ;vi'rZ; 

■:^M 

-■'■•■»■  V'i 

>•;:'..., -H' 

r.';^''-'      •■ 

101  g 


© 


?rt  Qi 


'& 


107  C 


Figs.  106-108. — Formation  of  spores  in  lower  fungi:  Fig.  106,  a  terminal  cell  of 
Saprolcgnia  producing  zoospores;  Fig.  107,  A-C,  three  stages  in  the  development  of 
the  sporangium  in  Mucor;  Fig.  108,  branches  of  the  sporophore  of  PcnidUium,  pro- 
ducing series  of  conidia.     From  Coulter,  etc.,  '10. 

While  these  forms  in  nature  usually  go  through  a  more  or  less 
definite  life  history  in  which  vegetative  growth  or  growth  with 
reproduction  of  new  vegetative  phytoids  occurs  for  a  time,  and  is 
followed  by  the  formation  of  spores  and  in  many  cases  still  later 

'  See  Klebs,  '93,  '96a,  '96^,  '98,  '99,  00(2,  'oo/>,  '03,  '04. 


250  SENESCENCE  AND  REJUVENESCENCE 

by  the  formation  of  gametes,  experiment  has  demonstrated  that  this 
Hfe  history  is  by  no  means  fixed  in  its'  course.  In  the  fungus 
Saprolegnia  mixta,  for  example,  which  occurs  on  the  bodies  of  dead 
insects  in  water,  Klebs  ('03,  p.  41)  has  found  that  uninterrupted 
v^egetative  growth  may  occur  for  an  indefinite  period  in  all  good 
nutritive  solutions,  provided  they  are  kept  fresh  and  do  not  under- 
go alteration.  On  the  other  hand,  a  rapid  and  complete  transforma- 
tion of  the  vegetative  form,  the  mycelium,  into  sporangia  occurs 
when  a  well-nourished  mycelium  is  transferred  from  the  nutritive 
solution  to  pure  water.  Growth  and  vegetative  reproduction, 
together  with  continuous  spore  formation,  occur  in  cultures  nour- 
ished on  agar-albumin  in  flowing  water.  When  mycehum  grown 
on  gelatin-meat  extract  is  transferred  to  water  and  allowed  to 
continue  its  growth  on  dead  insects,  growth  and  vegetative  repro- 
duction are  followed,  first,  by  formation  of  spores,  and  later  by 
gamete  formation.  In  water  containing  fibrin  or  syntonin  growth 
and  vegetative  reproduction,  formation  of  spores  and  of  gametes 
occur  together  on  different  parts  of  the  plant.  In  a  weak  solution 
of  haemoglobin,  growth  and  vegetative  reproduction  are  followed  by 
formation  of  gametes  and  later  by  formation  of  spores. 

Another  example  is  the  alga  Vaucheria  repens.  According  to 
Klebs  ('04,  p.  497),  the  following  conditions  induce  zoospore  forma- 
tion: decrease  of  the  salt-content  of  the  medium  to  a  point  near 
the  minimum  by  transference  from  more  to  less  concentrated  solu- 
tions, or  to  water;  increase  of  moisture  by  transference  from  air  to 
water;  decrease  of  the  oxygen  content  of  the  medium  by  trans- 
ference from  flowing  to  standing  water;  decrease  of  light  intensity, 
even  to  darkness;  lowering  of  temperature  to  near  the  minimum; 
increase  of  the  salt-content  to  near  the  maximum. 

Klebs  believes  that  external  conditions  produce  their  effects  on 
organisms  by  acting  upon  a  complex  of  internal  conditions,  and 
he  attempts  to  interpret  his  experimental  results  on  this  basis, 
pointing  out  that  many  of  the  conditions  which  induce  spore  forma- 
tion decrease  or  inhibit  growth,  i.e.,  vegetative  reproduction.  In 
this  way,  as  he  beheves,  a  higher  concentration  of  organic  substance 
is  attained  in  the  plant,  and  this  favors  spore  formation  and  a  still 
higher  concentration,  gametic  reproduction.     Apparently,  for  Klebs, 


AGE  CYCLE  IN  PLANTS  AND  LOWKR  AMM ALS 


2^1 


there  is  no  question  either  of  individuation  or  of  possible  age  changes 
involved,  the  reproductive  changes  being  due  primaril}-  to  the 
action  of  the  external  conditions. 

As  a  matter  of  fact,  however,  these  data  when  considered  in 
their  proper  relations  to  individuation  and  the  age  cycle  are  readily 
interpreted  and  are  directly  in  line  with  what  we  know  of  other 
forms.  Spore  formation  is,  at  least  in  most  cases,  a  more  speciaHzed 
reproductive  process  than  vegetative  reproduction,  and  therefore 
might  be  expected  to  occur  in  later  stages  of  development  than  the 
latter.  Moreover,  since  spore  formation  usually  consists  in  the  dis- 
integration into  single,  independent  cells  of  a  parent  body  or  part 
already  formed  rather  than  in  the  growth  of  a  new  individual  or 
part,  we  should  expect  it  to  occur  when  the  rate  of  metabolism  in 
the  plant  is  low  as  compared  with  the  rate  in  vegetative  growth  and 
reproduction.  Such  a  low  rate  of  metabolism  may  result,  either 
from  aging  of  the  individual  or  part,  or  from  the  action  of  external 
conditions.  If  the  conclusions  reached  from  the  study  of  the  lower 
animals  are  applicable  to  the  algae  and  fungi,  and  the  facts  seem 
to  indicate  that  they  are,  the  plant  under  certain  conditions  may 
remain  indefinitely  in  the  vegetative  condition,  because  the  differ- 
entiation and  senescence  in  each  individual  is  balanced  by  the 
rejuvenescence  occurring  in  each  vegetative  reproduction.  Under 
other  conditions  senescence  may  overbalance  rejuvenescence,  and 
the  plant  individuals  undergo  progressive  development  and  senes- 
cence, their  rate  of  metabolism  undoubtedly  decreases,  and  sooner 
or  later  the  disintegration  of  the  plant  or  parts  of  it  into  spores 
occurs.  The  results  of  Klebs's  experiments  indicate  that  this  con- 
dition may  be  induced  in  the  plant  cither  by  lowering  the  rate  of 
metabolism  directly  by  low  temperature,  lack  of  oxygen,  lack  of 
nutritive  salts,  etc.,  or  by  loading  the  cells  with  organic  material. 
While  it  is  impossible  from  the  data  at  hand  to  furnish  a  complete 
demonstration,  it  appears  highly  probable  that  the  effect  of  the 
various  conditions  used  by  Klebs  in  his  experiments  in  inducing 
spore  formation  is  either  to  bring  about  a  natural  senescence  in  the 
plant  by  the  accumulation  of  inactive  substances  or  to  decrease  its 
rate  of  metabolism  so  that  a  physiological  condition  like  that 
attained  in  natural  senescence  is  brought   about.     In   short,   by 


252  SENESCENCE  AND  REJUVENESCENCE 

controlling  the  rate  of  vegetative  reproduction,  the  rate  of  metab- 
olism, or  the  accumulation  of  inactive  material,  it  is  possible 
to  determine  whether  the  plant  or  the  phytoid  shall  remain  indeti- 
nitely  in  the  vegetative  stage  and  physiologically  young,  or  whether 
it  shall  attain  the  physiological  condition  characteristic  of  an  older 
plant  and  produce  spores.  There  are,  however,  certain  cases  which 
apparently  cannot  be  accounted  for  in  this  way:  for  example, 
Klebs  finds  that  when  the  alga  Oedogonium  is  cultivated  at  a  low 
temperature  a  rise  of  a  few  degrees  induces  spore  formation,  but 
when  cultivated  at  a  higher  temperature  a  rise  in  temperature  has 
no  such  effect.  As  regards  this  case,  it  is  probable  that  the  degree 
of  individuation  at  the  low  temperature  is  so  slight  that  when  an 
increase  in  metabolic  activity  occurs  with  a  rise  in  temperature  the 
cells  become  independent  before  their  activity  is  subordinated  or 
controlled  by  the  increased  degree  of  individuation. 

To  sum  up,  there  is  good  reason  to  believe  that  algae  and  fungi 
may  undergo  senescence  and  rejuvenescence  like  the  lower  animals, 
and  that  the  different  forms  of  reproduction  are  characteristic  of 
different  stages  in  the  life  cycle.  But  since  reproduction  and 
consequently  rejuvenescence  are  characteristic  of  younger  as  well 
as  older  stages,  it  is  possible  to  control  and  modify  the  course  of 
the  life  history  in  a  great  variety  of  ways.  This  possibility  of  con- 
trol does  not  prove  that  these  plants  have  no  definite  life  cycle: 
it  indicates  merely  that  progressive  and  regressive  development 
can  be  determined  experimentally  in  the  plant,  as  in  the  animal. 

As  regards  the  spores  themselves,  there  can  be  no  doubt  that 
extensive  reconstitution  and  rejuvenescence  occur  in  their  forma- 
tion. In  the  case  of  the  motile  zoospores  characteristic  of  many 
forms  (Figs.  104,  105,  106),  this  is  conspicuously  the  case,  for  the 
zoospore  is  a  free-living,  unicellular  organism  and  bears  Httle  resem- 
blance to  the  plant  from  which  it  arises.  This  new  individuation 
of  the  zoospore  from  the  physiologically  old  vegetative  stage 
involves  reconstitutional  changes  which  result  in  a  simpler  and 
more  primitive  kind  of  individual  than  the  vegetative  form.  This 
change  must  be  associated  in  some  way  with  the  change  from  the 
multicellular  or  multinucleate  to  the  unicellular  or  uninucleate 
condition.     In  the  development  of  the  vegetative  form  from  the 


AGE  CYCLE  IN  PLANTS  AND  LOWER  AMMALS  253 

spore,  reconstitutional  changes  are  again  involved,  at  least  in  the 
case  of  zoospores,  which  show  more  or  less  morphological  differen- 
tiation, and  here  again  some  degree  of  rejuvenescence  must  occur. 
Bearing  all  the  facts  in  mind,  it  is  not  difficult  to  understand  how 
it  is  that,  under  proper  conditions,  spore  formation  may  continue- 
through  an  indefinite  number  of  generations  without  any  appre- 
ciable progressive  senescence  of  the  stock. 

In  the  mosses,  ferns,  and  seed  plants  where  alternation  of  genera- 
tions occurs,  the  fertilized  egg  gives  rise  to  the  asexual  generation 
or  sporophyte  which  may  show  extensive  and  long-continued 
vegetative  reproduction,  but  sooner  or  later  gives  rise  to  spores. 
The  spore  in  turn  gives  rise  to  the  sexual  generation  or  gametophyte, 
which  also  may  show  vegetative  reproduction,  but  which  linally 
produces  gametes;  that  is,  sexual  reproductive  cells. 

In  the  mosses  and  ferns  spore  formation  is  very  evidently  a 
process  belonging  to  the  later  stages  of  development  of  the  sporo- 
phyte and  it  is,  as  in  the  algae  and  fungi,  a  process  of  disintegration 
of  an  individual  or  part  into  independent  cells.  In  the  fern,  for 
example,  the  spores  are  formed  only  when  the  frond  has  completed 
or  largely  completed  its  growth.  In  the  seed  plants  the  gameto- 
phyte generation  is  so  reduced  that  spore  formation  is  closely  con- 
nected with  the  formation  of  gametes,  and  there  is  much  evidence 
to  be  considered  in  later  chapters  which  indicates  that  gamete  for- 
mation belongs  to  a  more  advanced  stage  of  the  life  cycle  than  the 
various  agamic  processes.  In  these  plants,  as  in  the  algae  and  fungi, 
spore  formation  is,  then,  in  general  a  process  belonging  to  more 
advanced  stages  than  vegetative  reproduction. 

Among  algae  and  fungi  there  is  apparently  complete  rejuvenes- 
cence between  the  formation  of  the  spore  and  the  development  of  a 
new  plant  from  it,  for  it  usually  gives  rise  to  a  new  plant  like  that 
from  which  it  arose,  while  in  the  plants  with  alternation  of  genera- 
tions the  spore  gives  rise  to  an  individual  of  different  character 
from  that  which  produced  it.  Evidently  it  has  become  different 
in  its  developmental  capacity  from  the  egg.  The  simplest  concep- 
tion of  this  change  is  that  the  spore  is  in  these  forms  a  specialized 
cell  which  does  not  entirely  lose  its  specialization  in  reproduction. 
In    the   seed   plants,    where    the   gametophytes   do    not    lead    an 


254  SENESCENCE  AND  REJUVENESCENCE 

independent  vegetative  life,  but  are  usually  so  much  reduced  that 
only  a  few  cell  divisions  occur  between  the  spore  and  the  formation  of 
gametes,  the  specialization  of  this  reproductive  process  is  evident, 
but  in  the  mosses  where  the  sporophyte  is  merely  a  sporogonium — 
a  spore  case  without  an  independent  vegetative  life — and  the  game- 
tophyte  is  the  vegetative  form,  it  is  not  so  clear.  If,  however,  we 
consider  the  whole  cycle  from  the  fertilized  egg  of  one  generation  to 
that  of  the  next,  it  is  at  once  evident  that  in  the  mosses  the  process 
of  spore  formation  comes  relatively  early  in  this  cycle,  in  the  ferns 
at  a  more  advanced  stage,  and  in  the  seed  plants  at  a  still  more 
advanced  stage.  In  this  connection  it  is  of  considerable  interest 
to  note  that  the  amount  of  agamic  reproduction  in  the  gametophyte 
varies  according  to  the  point  in  the  life  cycle  at  which  the  gameto- 
phyte appears.  In  the  mosses,  where  the  sporophyte  shows  almost 
no  vegetative  activity  before  spore  formation,  the  gametophyte, 
which  is  the  moss  plant,  usually  shows  extensive,  often  indefinite, 
vegetative  reproduction,  and  in  many  cases  various,  more  or  less 
specialized,  forms  of  agamic  reproduction  occur.  In  the  ferns  where 
the  sporophyte — the  fern  plant — shows  extensive  vegetative  growth 
and  reproduction  there  is  usually  but  little  and  in  many  cases  no 
agamic  reproduction  in  the  prothallium  which  represents  the 
gametophyte.  And,  finally,  in  the  seed  plants,  where  the  whole 
vegetative  life  of  the  plant  occurs  in  the  sporophyte  stage,  the 
gametophyte  does  not  as  a  rule  reproduce  gametophytes  asexually. 
In  other  words,  the  earlier  in  the  life  cycle  the  gametophyte  appears, 
the  less  its  specialization  and  the  more  conspicuous  its  vegetative 
activity  and  reproduction. 

All  these  facts  indicate  very  clearly  that  a  real  life  cycle  with 
progressive  development  and  specialization  exists  in  the  plants, 
but  this  life  cycle  is  complicated  by  the  occurrence  of  various  forms 
of  agamic  reproduction,  and  the  regressive  and  reconstitutional 
changes  involved  in  the  new  individuations  which  occur  in  these 
reproductions  may  balance  the  progressive  changes  and  so  retard 
or  prevent  indefinitely  the  progressive  advance  of  the  plant  in  the 
life  cycle.  And  since  external  conditions  influence  individuation 
and  agamic  reproduction,  it  is  often  possible  to  control  experi- 
mentally the  developmental  progress  of  the  plant  within  very  wide 


AGE  CYCLE  IN  PLANTS  AND  LOWER  AMM ALS  2^? 

limits.  And,  finally,  there  are  certainly  very  clear  indications  that 
a  general  decrease  in  rate  of  metabolism,  doubtless  interrupted  Ijv 
greater  or  less  increases  in  rate  accompanying  the  various  reproduc- 
tions, occurs  from  the  early  vegetative  stages  to  the  stage  of  gamete 
formation.  There  seems,  in  short,  to  be  adequate  ground  for  the 
conclusion  that  the  life  cycle  of  the  plant  is  not  fundamentally 
different  from  that  of  the  animal  and  that  senescence  does  occur 
in  the  plant,  not  only  in  certain  cells,  organs,  or  tissues  and  in  the 
phytoids  which  make  up  most  plants,  but  in  the  plant  as  a  whole. 
The  slight  degree  of  individuation  in  plants  makes  possible  frequent 
reproduction,  so  that  senescence  is  not  a  continuous  or  nearly  con- 
tinuous process,  as  in  the  higher  animals,  but  may  be  interrupted 
repeatedly,  or  may  even  be  compensated  for  an  indefinite  length 
of  time  by  periodic  reproduction  and  rejuvenescence,  such  as  has 
been  shown  in  Part  II  to  occur  in  some  of  the  lower  animals. 

INDIVIDUATION,  AGAMIC  REPRODUCTION,  AND  THE  AGE  CYCLE  IX 

THE  LOWER  ANIMALS 

Experimental  evidence  on  the  relation  between  agamic  repro- 
duction and  rejuvenescence  in  various  animals  was  presented  in 
chap,  vi,  and  only  certain  points  of  more  general  significance  remain 
to  be  considered.  The  occurrence  of  agamic  reproduction  in  the 
lower  animals,  as  in  the  plants,  is  commonly  either  the  result  of 
growth  or  decreased  dominance,  and  often  the  same  reproductive 
process  may  be  brought  about  in  both  ways.  The  variety  of  forms 
of  reproduction  is  less  than  in  the  plant,  but  in  various  protozoa 
growth  and  division  occur  under  the  usual  conditions,  while  under 
others,  apparently  such  as  decrease  metabolism,  the  body  may 
break  up  into  small  independent  cells,  which  are  usually  known  as 
spores.  Such  fragmentations  of  the  body  may  apparently  result 
either  from  a  physiological  senescence  or  from  a  decrease  in  meta- 
bolic activity  due  to  external  conditions.  Fragmentation  often 
occurs  during  encystment  and  is  preceded  or  acconijianied  by 
complete  dedifferentiation  of  the  original  individual.  These  cases 
in  fact  constitute  some  of  the  strongest  evidence  for  the  occurrence 
of  dedifferentiation  in  animals.  Often,  particularly  in  the  sjxirozoa, 
which  are  parasitic  and  show  a  very  low  degree  of  indixiduation, 


256  SENESCE^XE  AND  REJUVENESCE\XE 

fragmentation  into  spores  follows  the  union  of  the  gametes  and 
may  probably  be  regarded  as  corresponding  to  the  period  of  cleavage 
and  rejuvenescence  in  the  embryonic  development  of  multicellular 
forms. 

In  many  sponges  new  zooids  arise  as  the  result  of  growth,  but 
under  depressing  conditions  and  probably  also  in  advanced  senes- 
cence, so  far  as  it  occurs,  existing  individuals  may  undergo  more  or 
less  extensive  fragmentation  into  cell  masses  known  as  gemmules 
which  are  capable  of  producing  new  sponge  bodies.  It  was  pointed 
out  in  chap,  vi  that  the  medusa  bud  of  the  hydroids  apparently 
results  from  a  decrease  in  dominance  which  is  associated  with  a 
decrease  in  rate  of  metabolism,  while  the  hydroid  bud  usually 
results  from  growth  beyond  the  limits  of  individuation.  In  certain 
of  the  bryozoa  also  budding  occurs  during  growth  and  a  partial 
fragmentation  into  reproductive  bodies,  the  statoblasts,  under 
depressing  external  conditions  and  apparently  also  in  advanced 
physiological  age.  On  the  other  hand,  in  Tuhularia  (p.  220),  in 
Planaria  (pp.  122-25),  ^^^  ^^  various  other  animals  the  same  form 
of  reproduction  may  result  either  from  growth  or  from  decrease 
in  dominance.  The  evidence  presented  in  chap,  vi  justifies  the 
conclusion  that  the  regressive  and  reconstitutional  changes  involved 
in  all  these  reproductive  processes  bring  about  a  greater  or  less 
degree  of  physiological  rejuvenescence. 

Reproduction,  however,  is  not  the  only  rejuvenating  process  in 
the  lower  animals.  Many  forms  undergo  encystment  or  become 
quiescent  under  conditions  which  do  not  permit  active  hfe  and 
become  active  again  after  a  certain  length  of  time,  or  when  external 
conditions  permit.  Usually  there  is  at  least  some  small  amount  of 
metabolic  activity  during  these  quiescent  periods,  and  a  consider- 
able degree  of  starvation  and  reduction  may  occur,  as  in  the  case 
of  Planaria  velata  (pp.  130-33),  before  resumption  of  active  life. 
The  effectiveness  of  reduction  as  a  rejuvenating  factor  in  pla- 
narians  has  been  demonstrated  in  chap,  vii,  and  it  certainly  plays 
a  similar  role  in  many  other  forms.  Moreover,  in  some  cases  the 
increase  in  number  of  individuals  or  the  decrease  in  supply  of 
nutrition  with  the  change  of  seasons  or  other  environmental  changes 
determines  more  or  less  regularly  recurring  periods  of  starvation 
during  active  life,  and  these  also  play  a  part  in  rejuvenescence. 


AGE  CYCLE  IX  PLANTS  AND  LOWER  AXLMALS  257 

And,  lastly,  the  replacement  of  old  by  young  cells  in  the  body  of 
the  animal  also  delays  the  senescence  of  the  organism  as  a  whole. 
This  process  occurs  more  or  less  widely  in  all  multicellular  animals, 
and  in  many  of  the  lower  forms  it  occurs  to  a  very  considerable 
extent  and  more  or  less  generally  throughout  the  body.  The  old 
cells  or  parts  die  and  are  either  cast  off  or  resorbed  and  replaced  by 
younger  cells.  In  such  cases  senescence  and  even  death  are  occur- 
ring at  all  times,  but  the  replacement  may  keep  pace  with  the 
aging  and  death  of  cells,  so  that  the  organism  as  a  whole  does  not 
grow  old.  Conditions  in  these  forms  are  somewhat  similar  to  those 
in  the  higher  plants  discussed  in  an  earlier  section  of  this  chapter, 
where  certain  parts  of  the  plant  remain  embryonic  and  give  rise 
more  or  less  continuously  or  periodically  to  the  various  organs 
which  undergo  senescence  and  death.  In  all  cases  of  this  sort  cel- 
lular reproduction  is  of  course  concerned  and  is  unquestionably  the 
essential  factor  in  the  maintenance  of  an  age  equilibrium  or  retarda- 
tion of  senescence  in  the  organism  as  a  whole. 

The  occurrence  in  animals  of  morphological  rejuvenescence,  i.e., 
of  dedifferentiation,  has  often  been  denied,  but  such  denials  are 
based  primarily  rather  on  theoretical  considerations  than  upon 
observation.  There  can  be  no  doubt  that  dedifferentiation  occurs 
extensively  among  the  lower  animals.  The  dedifferentiation  of 
protozoan  cells  has  already  been  mentioned,  and  concerning  those 
cases  there  is  no  room  for  doubt  that  the  morphological  ditTer- 
entiation  disappears  and  reappears  in  the  same  cell.  E.  Schultz 
('08)  and  J.  Nusbaum  ('12)  have  brought  together  many  cases  of 
dedifferentiation  from  the  literature  of  the  subject  and  have  dis- 
cussed their  significance  in  a  general  way.  It  is  impossible  here  to 
do  more  than  refer  very  briefly  to  a  few  of  the  well-established 
instances  of  dedifferentiation.  As  regards  the  sponges,  various 
authors  have  described  the  occurrence  of  dedilTerentiation  of  at 
least  some  of  the  cells  of  the  body  under  different  conditions,  such 
as  absence  of  lime  salts,  starvation,  and  dissociation  of  cells,  and 
there  seems  to  be  no  doubt  that  extensive  dedifferentiation  may 
occur  in  hydroids  also.'     One  of  the  most  interesting  cases  in  the 

'  See,  for  example,  on  sponges:  Bidder, '95;  Maas, '06, '07, '10;  Mastcrman, '94; 
K.  Muller,  'iia,  'iib,  'iir;  H.  V.  Wilson,  'iia;  on  hydroids:  Beminger,  '10;  H.  C. 
MuUer,  '13,  '14;   H.  V.  Wilson,  '116. 


258  SENESCENCE  AND  REJUVENESCENCE 

latter  group  is  that  described  by  H.  C.  Miiller,  of  the  dedifferentia- 
tion  after  isolation  and  mutilation  of  the  parts  which  bear  the 
sexual  organs — -the  so-called  gonophores — of  certain  hydroids  into 
masses  of  embryonic  cells  which  give  rise  to  stolons  and  so  may  pro- 
duce new  vegetative,  asexual  colonies.  Dedifferentiation  occurs 
in  the  reduction  by  starvation  of  planarians  (E.  Schultz,  '04).  The 
parenchymal  cells  of  Planaria,  which  play  the  chief  part  in  the 
formation  of  new  tissue  in  regeneration,  are  certainly  to  all  appear- 
ances differentiated  cells  and  undergo  dedifferentiation  when  they 
begin  their  growth  as  new  tissue.  In  the  tapeworm  Moniezia  the 
sex  cells  may  arise  by  the  dedifferentiation  of  parenchymal  cells 
(see  pp.  331-32).  The  return  of  old,  flat  ectoderm  cells  to  the 
embryonic  condition  has  been  observed  by  Romer  ('06)  in  the 
regeneration  of  bryozoa.  Krahelska  ('13)  has  described  the 
dedifferentiation  of  the  albumen  gland  in  certain  snails  during 
oviposition.  In  the  remarkable  reduction  of  the  branchial  region 
in  isolated  pieces  of  the  ascidian  Clavellina,  which  represents  a 
return  to  the  condition  of  a  bud  in  an  early  stage  of  development, 
extensive  dedifferentiation  of  cells  certainly  occurs  (Driesch,  '02; 
E.  Schultz,  '07).  Schaxel  ('14),  however,  maintains  that  in  this 
case  the  differentiated  cells  are  lost  and  the  new  parts  arise  from 
undifferentiated  cells  which  remain,  but  his  assumption  that  the 
cells  which  take  part  in  the  new  development  are  undifferentiated 
is  not  proved.  In  the  regeneration  of  the  lens  of  the  eye  in 
amphibia  the  cells  of  the  iris  which  give  rise  to  the  new  lens  very 
evidently  undergo  dedifferentiation  (G.  Wolff,  '95;  Fischel,  '00). 
Numerous  other  cases  of  more  or  less  complete  dedifferentia- 
tion have  been  more  or  less  closely  observed  and  described  and 
doubtless  many  others  still  remain  to  be  described  in  connection 
with  agamic  reproduction,  reconstitution,  and  even  in  the  normal 
life  of  organisms.  The  changes  in  gland  cells  during  their  cycle  of 
activity  (pp.  189-91)  and  various  other  periodical  changes  also 
belong  in  this  category.  But  the  morphological  criterion  of  reju- 
venescence is  at  best  unsatisfactory,  for  it  is  merely  a  rather  unre- 
liable indicator  of  the  physiological  condition  of  the  cells.  As  is 
evident  from  the  experimental  study  of  the  developmental  stages 
of  many  animals,  cells  may  undergo  considerable  changes  in  the 


AGE  CYCLE  IN  PLANTS  AND  LOWER  ANLMALS  259 

direction  of  specialization  without  any  characteristic  morpho- 
logical differentiation,  and  there  is  every  reason  to  believe  that 
changes  in  the  opposite  direction,  if  not  very  great,  do  not  neces- 
sarily involve  changes  in  the  visible  morphological  features  of  the 
cell.  Since  senescence  and  rejuvenescence  are  processes  which 
concern  the  dynamic  activity  of  the  cell,  changes  in  this  activity 
must  be  the  chief  criterion  for  the  occurrence  of  age  changes, 
although  morphological  changes,  when  they  occur,  may  be  of  value 
as  indications  of  the  changes  in  activity. 

SENESCENCE  AS  A  CONDITION  OF  REPRODUCTION  AND 
REJUVENESCENCE 

Agamic  reproduction  of  one  kind  or  another  unquestionably 
occurs  in  the  plants  and  lower  animals  in  consequence  of  the  decrease 
or  elimination  of  dominance,  i.e.,  the  physiological  disintegration 
of  the  individual  may  result  in  the  reconstitution  of  new  individuals. 
]\Ioreover,  decrease  or  elimination  of  dominance  may  result  from 
decrease  in  rate  of  metaboHsm  as  well  as  from  growth,  and 
finally  a  decrease  in  rate  of  metabolism  occurs  in  senescence.  It  is 
possible,  therefore,  that  agamic  reproduction  with  the  accompa- 
nying rejuvenescence  may  occur  simply  as  the  result  of  senescence. 
The  fragmentation  of  Planaria  velata  (pp.  130-33)  is  undoubtedly 
a  case  of  this  sort,  and  it  is  probable  that  this  relation  between 
senescence  and  reproduction  is  very  general.  In  fact,  the  forma- 
tion of  spores  in  plants  and  in  the  protozoa,  of  gemmules  in  the 
sponges  and  statoblasts  in  the  bryozoa,  and  various  other  reproduc- 
tive processes,  which  are  not  directly  connected  with  growth,  are 
probably  very  often  simply  the  result  of  senescence  of  the  indi- 
vidual concerned,  although  they  may  of  course  appear  when  the 
rate  of  metaboHsm  is  lowered  by  external  conditions.  The  forma- 
tion or  development  of  new  buds  in  many  perennial  plants  often 
results  from  decrease  in  activity  of  the  dominant  growing  tip.  and 
this  decrease  is  probably  very  frequently  due  to  senescence.  The 
formation  of  buds  or  the  development  of  buds  already  formed  on 
the  leaves  of  various  plants  may  likewise  result  from  senescence  of 
the  leaf  or  plant.  During  the  earlier  stages  of  senescence  disinte- 
gration of  the  individual  may  be  prevented  by  the  develoj^ment  and 


26o  SENESCENCE  AND  REJUVENESCENCE 

increasing  conductivity  of  the  paths  of  correlation,  even  though 
increase  in  size  occurs,  but  in  the  lower  organisms  where  the  degree 
of  dominance  is  slight  and  conduction  paths  do  not  attain  any  high 
degree  of  development,  the  decrease  in  rate  of  metabolism  in  the 
dominant  region  which  occurs  with  advancing  senescence  may 
sooner  or  later  bring  about  the  physiological  isolation  of  parts  of 
the  individual,  and  reproduction  and  rejuvenescence  result.  Ex- 
tended experimental  and  analytic  investigation  is  necessary  to 
determine  how  far  a  natural  physiological  senescence  and  how  far 
incidental  or  external  factors  are  concerned  in  particular  cases, 
but  it  must  be  borne  in  mind  that  the  possibility  of  inducing  and 
controlling  these  reproductions  with  the  aid  of  external  conditions 
does  not  in  any  way  prove  that  they  may  not  also  be  induced  or 
controlled  by  internal  conditions  quite  independently  of  the 
environment. 

Since  this  relation  between  senescence  and  reproduction  unques- 
tionably exists,  it  is  evident  that  in  the  plants  and  lower  animals 
senescence  must  very  frequently  lead  automatically  to  reproduction 
and  rejuvenescence  in  at  least  some  parts  of  the  previously  existing 
individual.  In  such  cases  senescence  does  not  lead  to  death  of  the 
whole,  and  often  where  the  individual  breaks  up  into  separate  cells 
or  fragments,  death  does  not  occur  in  any  part.  Instead  of  leading 
inevitably  to  death,  senescence  in  the  lower  organisms  may  itself 
be  a  condition  of  reproduction  and  rejuvenescence  and  so  of  indefi- 
nite continuation  of  life. 

CONCLUSION 

In  the  plants  and  lower  animals  the  low  degree  of  stabihty 
of  the  protoplasmic  substratum  and  the  consequent  low  degree  of 
individuation  make  possible  the  frequent  occurrence  of  agamic 
reproduction.  Since  a  greater  or  less  degree  of  rejuvenescence  is 
associated  with  such  reproduction,  the  process  of  individual  senes- 
cence may  be  more  or  less  completely  compensated  in  many  cases 
and  the  organism  may  appear  not  to  grow  old  and  may  never  reach 
the  death  point.  Often  the  decrease  in  metabolic  rate  with  ad- 
vancing senescence  is  the  primary  factor  in  bringing  about  physio- 
logical isolation  of  parts,  reproduction,  and  rejuvenescence,  and  in 


AGE  CYCLE  IN  PLANTS  AND  LOWER  ANIMALS  261 

such  cases  a  certain  degree  of  senescence  is  followed  aulomatically 
by  reproduction  and  rejuvenescence.  The  agamic  reproductions  of 
advanced  age  are  often  more  highly  specialized  in  character  than 
those  of  earlier  periods  of  the  life  history. 

Senescence  may  be  retarded  or  compensated  in  many  forms  by 
conditions  which  induce  frequent  agamic  reproduction,  while  under 
other  conditions  senescence  may  be  accelerated  and  death  may 
occur.  The  relation  between  senescence  and  rejuvenescence  de- 
termines whether  an  organism  undergoes  progressive  senescence 
and  passes  through  a  definite  life  history  or  persists  indefinitely  in  a 
certain  physiological  condition,  apparently  without  a  definite  life 
cycle. 

REFERENCES 
Benedict,  H.  M. 

191 2.     "Senility  in  Meristematic  Tissues,"  Science,  XXXV. 

1915.     "Senile  Changes  in  the  Leaves  of  Vitis  vulpina  and  Certain  Other 

Perennial  Plants":  Proc.  of  Bot.  Soc.  of  America,  Science,  XLI. 

Berxinger,  J. 

1910.     "Einwirkung  von  Hunger  auf  Hydra,'"  Zool.  Anzeiger,  XXXX'L 

Bidder,  G.  P. 

1895.     "The  Collar  Cells  of  Heterocoela,"  Quart.  Jour,  of  Micr.  Sci., 

XXXVHI. 

Brefeld,  O. 

1876.  "Die  Entwicklungsgeschichte  der  Basidiomyceten,"  Bot.  Zeitg., 
XXXIV. 

1877.  Botanische  Untersuchungen  iiber  Schimmelpilze,  III. 
Burns,  G.  P.,  and  Heddon,  Mary  E. 

1906.     "Conditions   Influencing   Regeneration   of   Hypocotyl,"   Beihejte 
z.  Bot.  Centralbl,  XIX,  Abt.  I. 
Coulter,  J.  M.,  Barnes,  C.  R.,  and  Cowles,  H.  C. 

1910.     A  Textbook  of  Botany.     New  York. 
DiELS,  L. 

1906.    Jugefidfonnen  und  Blutenreije  int  Pflanzenreich.    Berlin. 
Driesch,  H. 

1902.  "Studien  iiber  das  Regulationsvermogen  der  Organismen:  \'I, 
Die  Restitutionen  von  ClavcUina  lepadijormis;  Cbcr  cin  neucs 
harmonisch-aquipotentielles  System  und  iiber  solche  Systemc 
iiberhaupt,"  Arch.  f.  Entwickclungsmcch.,  Xl\'. 

Faber,  F.  C,  von. 

1908.  "Uber  Verlaubung  von  Cacaobliiten, "  Berichtc  d.  dcutscli.  bot. 
Ges.,  XXV. 


262  SENESCENCE  AND  REJUVENESCENCE 

FiSCHEL,  A. 

1900.     "IJber  die  Regeneration  der  Linse,"  Anat.  Hefte,  XLIV. 

Fitting,  H. 

1907.  "Die  Reizleitungsvorgange  bei  den  Pflanzen,"  Sonderabdr.  aus 
Ergebn.  d.  Physiol.,  Jhg.  IV  und  V. 

GOEBEL,  K. 

1908.  Einleitung  in  die  experimenielle  Morphologic  der  Pflanzen.     Leipzig. 

Heim,  C. 

1896.     "  Untersuchungen  an  Farnprothallien,"  Flora,  LXXXII. 

HiLDEBRAND,  F. 

1910.  "Umanderung  einer  Bliitenknospe  in  einen  vegetativen  Spross 
bei  einem  Phyllocactus,"  Berichte  d.  deutsch.  hot.  Ges.,  XXVIII. 

JOST,  L. 

1908.     Vorlesungen  iiber  Pflanzcnphysiologie.     II.  Auflage.     Jena. 

Klebs,  G. 

1893.     "tJber  den  Einfluss  des  Lichtes  auf  die  Fortpflanzung  der  Ge- 

wachse,"  Biol.  Centralbl.,  XIII. 
1896a.  Die  Bedingnngen  der  Fortpflanzung  bei  einigen  Algen  und  Pilzen. 

Jena. 
18966.   tJber  die  Fortpflanzungsphysiologie  der  niederen  Organismen.     Jena. 

1898.  "Zur  Physiologic  der  Fortpflanzung  einiger  Pilze:  I,  Sporodinia 
grandis,"  Jahrbilcher  J.  wiss.  Bot.,  XXXII. 

1899.  "Zur  Physiologic,  etc.:  II,  Saprolegnia  mixta,''  JahrbUcher  f.  wiss. 
Bot.,  XXXIII. 

1900a.  "Zur  Physiologic,  etc.:  Ill,  Allgemeinc  Betrachtungen,"  Jahr- 
bUcher f.  wiss.  Bot.,  XXXV. 

i90oZ>.  "Einige  Ergebnissc  der  Fortpflanzungsphysiologie,"  Berichte  d. 
deutsche.  bot.  Ges.,  XVIII. 

1903.  W illkiirliche  Entwicklungsdndenmgen  bei  Pflanzen.     Jena. 

1904.  "tJber  Problcme  der  Entwicklung,  Biol.  Centralbl.,  XXIV. 
1906a.  tJber  kiinstliche  Metamorphosen.     Stuttgart. 

19066.   "tJber  Variation  der  Bliiten,"  Jahrbilcher  f.  wiss.  Bot.,  XLII. 

KOHLER,  P. 

1907.  "Beitragc  zur  Kenntnis  der  Reproduktions-  und  Regenerations- 
vorgange  bei  Pilzen,  etc.,"  Flora,  XCVII. 

Krahelska,  Marie. 

1913.  "Drlisenstudien.  Histologischer  Bau  der  Schneckeneiweissdriise 
und  die  in  ihm  durch  Einfluss  des  Hungers,  der  funktioncUen 
Erschopfung  und  der  Winterruhe  hervorgerufcnen  Verande- 
rungen,"  Arch.  J.  Zellforsch.,  IX. 

Kreh,  W. 

1909.  "tJber  die  Regeneration  der  Lebermoose,"  Nova  Acta;  Abh.  d. 
Kais.  Leap.  Carol,  deutschen  Akad.  d.  Naturforscher,  XC. 


AGE  CYCLE  IN  PLANTS  AND  LOWER  AM.MALS  263 

Maas,  O. 

1906.  "tJber  die  Einwirking  karbonatfreier  Salzlosungen  auf  cnvachsenc 
Kalkschwamme  unci  auf  Enlwicklungssladicn  derselbcn,"  Arc/i. 
f.  Entwickelungsmech.,  XXII. 

1907.  "tJber  die  Wirkung  des  Hungers  und  Kalkcntzichung  bei  Kalk- 
schwammen  und  anderen  kalkausschcidenden  Organismen." 
Sitzungsber.  d.  Gesell.  f.  Morphol.  u.  Physiol.     Miinchen. 

1910.  "ijber  Involutionserschcinungen  bei  Schwiimmcn  und  ihrc  Bcdeu- 
tung  fur  die  Auflassung  des  Spongienkorpers,"  Fcstsc/ir.  z.  60. 
Geburtstag  R.  Hertwigs,  Bd.  III. 

Magnus,  W. 

1906.     "tJber  Formbildung  der  Hutpilze,"  Arch.f.  Biontologie,  I. 

Masterman,  a.  J. 

1894.  "On  the  Nutritive  and  Excretory  Processes  in  Porifera,"  Ann. 
and  Mag.  of  Nat.  Hist.,  (6),  XIII. 

MiEHE,  H. 

1905.  "Waschstum,  Regeneration  und  Polaritat  isolierter  Zellen," 
Berichte  d.  deutsch.   hot.   Ges.,  XXIII. 

MtJLLER,  H.  C. 

1913.  "Die  Regeneration  der  Gonophore  bei  den  Hydroiden  und  an- 
schliessende  biologische  Beobachtungcn:  I,  Athecata,"  Arch.  f. 
Entwickelungsmech.,  XXXVII. 

1914.  "Die  Regeneration,  etc.:  II,  Thecata,"  Arch.  f.  Entwickelungs- 
mech., XXXVIII. 

MiJLLER,  K. 

191  ifl.  "Beobachtungen  iiber  Reduktionsvorgange  bei  Spongilliden," 
Zool.  Anzeiger,  XXXVII. 

191 16.  "Das  Regenerationsvermogen  der  Siisswasserschwamme,  insbeson- 
dere  Untersuchungen  iiber  die  bei  ihnen  vorkommende  Regenera- 
tion nach  Dissociation  und  Reunition,"^rc/(./.  Entwickelungsmech., 
XXXII. 

1911C.  " Reduktionserscheinungen  bei  Siisswasserschwammen,"  .irch.  f. 
Entwickelungsmech. ,  XXXII. 

Nicolas,  G. 

1909.  "Recherches  sur  la  respiration  des  organcs  vegelatifs  des  plantes 
vasculaires,"  Ann.  des  sci.  nat.  Bot.,  (9),  X. 

1910.  "Sur  variations  de  la  respiration  des  vegetaux  avec  Tago,"  Bull. 
Sac.  hist.  nat.  Afrique  du  Nord. 

Noll,  F. 

1903.  "Beobachtungen  und  Betrachtungen  iiber  embryonale  Subslanz," 
Biol.  Centralbl.,  XXIII. 


264  SENESCENCE  AND  REJUVENESCENCE 

NUSBAUM,  J. 

191 2.  "Die  entwicklungsmechanisch-metaplastischen  Potenzen  der  tieri- 
schen  Gewebe,"  Vortr.  mid  Aufs.  ii.  Entwickelungsmech.,  XVII. 

Pfeffer,  W. 

1897.     Pflanzenphysiologie.     II.  Auflage.   I.  Bd. 

Kegel,  F. 

1876.  "Die  Vermehrung  der  Begoniaceen  aus  ihren  Blattern,"  Jen. 
Zeitschr.f.  Naturwissenschaften,  X. 

RiEHM,  E. 

1905.  "Beobachtungen  an  isolierten  Blattern,"  Zeitschr.  /.  Naturwis- 
senchaften,  LXXVII. 

ROMER,    O. 

1906.  "  Untersuchungen  uber  die  Knospung,  Degeneration  und  Regenera- 
tion von  einigen  marinen  entoprokten  Bryozoen,"  Zeitschr.  f.  wiss. 
Zool.,  LXXXIV. 

SCHAXEL,  J. 

1914.  "Reduktion  und  Wiederauffrischung,"  Verhaiidlungen  d.  deutsch. 
zool.  Gesell. 

SCHOSTAKEWaxSCH,  W. 

1894.  "tJber  die  Reproduktions-  und  Regenerationsercheinungen  bei  den 
Lebermoosen,"  Flora,  LXXIX. 

SCHULTZ,  E. 

1904.  "t)ber  Reduktionen:  I,  tlber  Hungererscheinungen  bei  Planaria 
laclea,"  Arch.  f.  Entwickelungsmech.,  XVIII. 

1907.  "Uber  Reduktionen:  III,  Die  Reduktion  und  Regeneration  des 
abgeschnittenen  Kiemenkorbes  von  Clavellina  lepadiformis," 
Arch.  f.  Entwickelungsmech.,  XXIV. 

1908.  "tJber  umkehrbare  Entwickelungsprozesse  und  ihre  Bedeutung 
fiir  eine  Theorie  der  Vererbung,"  Vortr.  und  Aufs.  u.  Entwickelungs- 
mech., IV. 

TOBLER,  F. 

1902.     "Zerfall  und  Reproduktionsvermogen  des  Thallus  einer  Rhodo- 

melaceae,"  Berichte  d.  deutsch.  hot.  Ges.,  XX. 
1904.     "tJber  Eigenwachstum  der  Zelle  und  Pflanzenform,"  Jahrhiicher 

f.  wiss.  BoL,  XXXIX. 

VOCHTING,  H. 

1885.     "tJber  die  Regeneration  der  Marchantieen,"  Jahrhiicher  f.  wiss. 

BoL,  XVI. 
1887.     "iJber  die  Bildung  der  Knollen,"  Bihliotheca  hot.,  H.  4. 
1900.     "Zur  Physiologie  der  Knollengewachse,"  Jahrhiicher  f.  wiss.  Bot., 

XXXIV. 


AGE  CYCLE  IN  PLANTS  AND  UJWER  ANIMALS  265 

Wilson,  H.  V. 

1911a.  "Development  of  Sponges  from  Dissociated  Tissue  Cells,"  Bull 

of  the  Bureau  of  Fisheries,  XXX. 
191 1^*.  "On    the    Behavior    of    Dissociated    Cells    in    the     Hydroids, 
Alcyonaria  and  Asierias,"  Jour,  of  Exp.  ZooL,  XL 
Winkler,  H. 

1902.     "ijber  die  nachtriigliche  Umwandlung  von  Bluthenbliittern  und 

Narben  in  Laubbliitter,"  Berichte  d.  deutsch.  bat.  Ges.,  XX. 
1907.     "tJber  die  Umwandlung  des  Blattstiels  zum  Stengel,"  JahrbiUhcr 
f.  wiss.  BoL,  XLV. 
Wolff,  G. 

1895.     "Entwickelungsphysiologische    Studien:      1,     Regeneration    dcr 
Urodelenlinse,"  Arch.f.  Entwickelungsmech.,  I. 


CHAPTER  XI 
SENESCENCE  IN  THE  HIGHER  ANIMALS  AND  MAN 

The  problem  of  senescence  in  man  and  the  higher  animals  has 
very  naturally  claimed  the  attention  of  the  anatomist,  the  physiolo- 
gist, the  investigator  along  medical  Knes,  and  the  zoologist,  and  for 
the  layman  also  it  has  always  possessed  a  vital  interest  quite  differ- 
ent from  that  which  attaches  to  many  scientific  problems.  Man's 
interest  in  the  problem  of  his  own  senescence,  old  age,  and  death 
undoubtedly  dates  from  the  time  when  he  first  began  to  think  and 
ask  himself  questions  concerning  himself.  From  ancient  times  to 
the  present  the  problem  has  been  discussed  again  and  again,  and 
from  the  most  various  points  of  view.  It  has  always  been  an 
attractive  field  for  speculation,  but  a  large  volume  of  scientific 
data  bearing  upon  one  aspect  or  another  of  it  has  accumulated. 
A  considerable  portion  of  the  literature  of  the  subject  deals  with 
the  problem  from  the  point  of  view  of  the  physician  and  medical 
investigator  rather  than  that  of  the  general  zoologist  or  physiolo- 
gist, and  of  course  the  data  are  very  largely  descriptive  and 
statistical,  rather  than  experimental  and  analytic. 

It  is  neither  possible  nor  necessary  at  this  time  to  attempt  any 
extended  review  and  critique  of  the  literature.  My  purpose  is 
merely  to  analyze  and  interpret  the  more  important  facts  from  the 
point  of  view  attained  through  study  of  the  lower  animals,  and  to 
show  how  the  age  cycle  in  man  and  the  higher  animals,  so  far  as  it 
differs  from  that  in  the  lower  organisms,  is  the  necessary  and  inevi- 
table result  of  the  course  of  evolution. 

INDIVIDUATION  AND  REPRODUCTION  IN  THE  HIGHER  FORMS  IN 
RELATION  TO  THE  AGE  CYCLE 

The  increase  in  the  degree  of  individuation  or  physiological 
integration  of  the  individual,  which  is  a  conspicuous  feature  of 
evolution,  is  evident  in  the  higher  animals  and  man  in  the  increasing 
co-ordination  and  interrelation  of  parts,  both  dynamically  and 
chemically,  and  in  the  greater  structural  and  functional  specializa- 
tion and  differentiation.     The  problem  of  the  nature  of  this  change 

266 


SENESCENCE  IN  HIGHER  ANIMALS  AND  MAX  267 

and  the  factors  concerned  in  it  is  of  course  the  problem  of  the  evo- 
lution of  the  individual,  but  only  certain  aspects  of  this  problem 
need  consideration  here. 

The  evolution  of  the  individual  is  evidently  closely  associated 
with  an  increasing  functional  and  structural  stability  of  protoplasm. 
In  the  higher  forms  a  cell  or  a  group  of  cells,  once  started  along  a 
certain  course  of  development,  reacts  less  readily  than  in  the  lower 
organisms  to  altered  conditions  by  regression  and  change  in  the 
course  of  development.  In  the  adult  vertebrates  the  capacity  for 
regression  is  in  most  cases  so  narrowly  limited  that  the  cells  of  one 
tissue  are  under  any  known  conditions  incapable  of  giving  rise  to 
other  tissues.  In  other  words,  the  ability  of  the  cells,  so  conspicu- 
ous in  the  lower  organisms,  to  react  to  altered  conditions  by  a  change 
in  activity  which  brings  about  the  breakdown  and  elimination  of 
previously  accumulated  structural  substance  is  very  slight  in  the 
higher  animals.  From  this  point  of  view  evolution  appears  as  a 
change  from  less  stable  to  more  stable  dynamic  equilibrium,  in  the 
course  of  which  the  morphogenetic  and  functional  behavior  of  the 
organism  has  become  less  directly  dependent  on  external  and  more 
dependent  on  internal  conditions.  This  increase  in  structural  and 
functional  stability  results  in  a  greater  degree  of  continuity  in 
progressive  development  and  so  in  a  greater  specialization  of  parts 
and  a  greater  differentiation  of  structural  mechanisms  with  definite 
functions,  which  in  turn  provide  a  basis  for  a  more  varied  and 
intimate  correlation  of  parts  and  so  for  a  wider  range  and  greater 
delicacy  of  functional  adjustment. 

Among  these  changes  the  most  important  for  the  integration  of 
the  individual  are  the  functional  and  structural  evolution  of  the 
nervous  system.  The  high  metabolic  rate  in  the  cells  of  the  cen- 
tral nervous  system  undoubtedly  determines  that  the  accumulation 
and  transformation  of  substance  in  the  structural  substratum 
which  bring  about  senescence  occur  less  rapidly  here  than  in  other 
tissues;  because  of  its  high  rate  of  metabolic  flow,  the  ners'e  cell 
deposits  structural  sediment  relatively  slowly.  This  is  particularly 
true  after  the  stage  of  specialized  functional  activity  is  attained, 
for  then  stimulation  through  the  sense-organs  and  other  parts  of 
the  body  plays  a  very  important  part  in  maintaining  the  ner\-e 


268  SENESCENCE  AND  REJUVENESCENCE 

cell  at  a  very  high  metabolic  level.  Consequently  the  degree  of 
dominance  and  of  individuation  may  increase  up  to  a  certain  point 
as  development  proceeds.  Moreover,  the  increasing  differentiation 
of  the  nerve  fibers  determines  a  more  effective  conduction  of  im- 
pulses, and  the  increasing  centralization  of  the  nervous  system  and 
complexity  of  nervous  correlation  results  in  a  greatly  increased 
unity  and  co-ordination  of  the  parts  of  the  individual.  It  was 
pointed  out  in  chap,  ix  that  the  decrement  in  the  conduction  of 
impulses  in  the  nerves  of  the  higher  animals  is  scarcely  appreciable 
within  the  limits  of  the  individual  body.  This  means  that  in  the 
adult  the  limit  of  dominance,  the  physiological  limit  of  individ- 
uation, is  far  beyond  the  actual  size  attained  by  the  individual. 
Growth  in  these  forms  is  limited  by  progressive  differentiation,  con- 
sequently the  final  size  of  the  individual  remains  far  below  the  limit 
of  dominance  in  the  differentiated  nervous  system,  and  the  physio- 
logical isolation  of  parts  so  frequent  among  the  plants  and  lower 
animals  does  not  occur  under  ordinary  conditions  in  the  higher  ani- 
mals after  the  functional  capacity  of  the  nervous  system  has  fully 
developed. 

For  the  occurrence  of  agamic  reproduction  in  differentiated 
organisms  the  physiological  or  physical  isolation  of  a  part  and 
capacity  of  the  part  to  react  to  isolation  by  regression  and  recon- 
stitution  are  necessary.  These  conditions  are  not  present  in  the 
later  stages  of  development  of  the  higher  animals,  but  isolation  of 
parts  does  occur  to  a  limited  extent  in  early  stages  of  development 
before  the  cells  have  undergone  appreciable  differentiation  and  be- 
fore the  individual  has  attained  the  degree  of  integration  character- 
istic of  later  stages.  Consequently  agamic  reproduction  in  these 
forms  is  limited  to  these  stages.  In  a  few  species  polyembryony 
occurs  as  a  normal  feature  of  development,  the  egg  undergoing 
separation  during  cleavage  or  later  embryonic  stages  into  two  or 
more  individuals.  In  certain  parasitic  insects,  for  example,  indi- 
viduation is  apparently  almost  entirely  absent  during  early  stages 
and,  instead  of  developing  in  an  orderly  way  as  a  single  embryo, 
the  eggs  as  they  divide  separate  repeatedly  into  cells  or  cell  groups, 
each  of  which  finally  gives  rise  to  an  embryo  (P.  Marchal,  '04; 
Silvestri,  '06).     In  these  cases  a  single  egg  may  give  rise  to  a  large 


SENESCENCE  IN  HIGHER  ANIMALS  AM)  MAX  269 

number  of  individuals.  In  the  nine-banded  armadillo  the  embryo 
begins  development  as  a  single  embryo,  but  later  undergoes  recon- 
stitution  into  four  embryos  by  a  process  of  budding  (Patterson.  '13). 
In  other  species  of  armadillo  a  similar  process  of  embryonic  repro- 
duction undoubtedly  occurs.  The  cases  of  duplicate  twins  and 
various  forms  of  double  monsters  are  probably  also  cases  of  embr>'- 
onic  reproduction  from  a  single  egg  (Wilder,  '04),  but  it  is  not 
certainly  known  at  what  stage  the  reproduction  occurs. 

In  addition  to  the  occasional  occurrence  of  polyembryony  the 
process  known  as  segmentation  occurs  as  a  characteristic  feature 
of  development  in  all  the  higher  animals,  both  invertebrates  and 
vertebrates.  Segmentation,  however,  is  rather  a  repeated  indi- 
viduation of  parts  from  embryonic  tissue  than  a  reproduction  from 
differentiated  cells,  and  does  not  therefore  involve  any  considerable 
regression  and  reconstitution.  The  segment-individuals  which  arise 
in  succession  as  morphogenesis  proceeds  posteriorly  along  the  a.\is 
(see  Figs.  70,  197,  198)  never  complete  development  to  whole 
animals,  but  remain  as  segments  subordinate  to  the  dominating 
head-region.  Aside  from  these  cases  of  polyembryony  and  repeti- 
tive formation  of  segments,  agamic  reproduction  plays  no  part  in 
the  normal  life  historv  of  the  higher  animals,  and  it  is  evident  that 
these  reproductions,  since  they  occur  so  early  in  development,  can 
have  but  little  significance  in  bringing  about  rejuvenescence  or 
retarding  the  progressive  course  of  senescence. 

A  most  important  consequence  of  the  stability  of  structure  and 
the  absence  of  agamic  reproduction  in  these  animals  is  the  greater 
continuity  of  progressive  development  and  senescence.  In  the 
lower  forms  progressive  development  may  be  interrupted  repeat- 
edly, or  even  periodically  completely  compensated,  b\'  agamic 
reproduction  of  one  kind  or  another  with  its  accompanying  rejuve- 
nescence. Where  such  reproduction  is  absent  the  regressive  changes 
may  occur  to  some  extent  in  tissue  regeneration,  in  the  periodic 
elimination  of  previously  accumulated  material  in  gland  cells 
(see  pp.  189-91),  or  during  starvation,  and  under  certain  other 
conditions  which  bring  about  excessive  structural  breakdown,  but 
such  changes  are  either  narrowly  localized  and  without  apjire- 
ciable  effect  upon  the  body  as  a  whole,  or  they  are  so  slight  that  it 


2  70  SENESCENCE  AND  REJUVENESCENCE 

is  a  question  whether  they  can  properly  be  called  rejuvenescence, 
or  else  they  bring  about  death  before  any  great  degree  of  rejuvenes- 
cence occurs,  so  that  in  such  animals  hfe  after  the  early  embryonic 
stages  is  practically  a  continuous  progression  and  senescence.  Such 
a  continuous  progressive  development  and  senescence  without 
counterbalancing  regression  and  rejuvenescence  must  inevitably 
and  necessarily  terminate  sooner  or  later  in  death  in  consequence 
of  decrease  in  rate  of  metabolism.  From  this  point  of  view,  then, 
the  increasing  continuity  of  senescence  and  the  appearance  of  death 
as  a  natural  termination  of  development  in  the  course  of  evolution 
from  the  lower  to  the  higher  animals  are  to  a  large  degree  the  con- 
sequence of  the  increasing  fixity  or  stability  of  the  structural  sub- 
stratum of  the  organism  which  determines  on  the  one  hand  the 
increasing  degree  of  individuation  and  on  the  other  the  limitation 
of  regression  and  reproduction. 

But  in  the  course  of  this  life  history  which  ends  in  death,  sexual 
differentiation  appears,  and  at  a  certain  stage  of  development  the 
individuals  of  each  sex  or  the  organs  of  each  sex  in  a  hermaphroditic 
individual  give  rise  to  the  gametes  which  are  highly  specialized, 
sexually  differentiated  cells,  the  egg  and  the  spermatozoon.  These 
cells  are  cast  off  from  the  body  which  produced  them  like  other  cells 
which  have  completed  their  developmental  history  and  grown  old, 
and  in  most  cases  they  do  not  react  to  the  isolation  by  regression, 
rejuvenescence,  and  reconstitution  of  a  new  individual,  but  sooner 
or  later  die,  unless  union  between  two  gametes  of  opposite  sexes, 
that  is,  fertilization,  occurs.  This  union,  when  it  does  occur,  initi- 
ates in  some  way  the  process  of  regression  and  rejuvenescence  in 
the  resulting  cell,  the  zygote,  and  the  reconstitution  of  a  new  indi- 
vidual, or  what  we  call  embryonic  development,  occurs.  The 
gametes  are  the  only  cells  in  the  higher  animals  which  undergo 
complete  rejuvenescence  and  so  escape  death.  This  conception 
of  gametic  reproduction  will  be  considered  more  at  length  in  Part  IV. 

THE  PROCESS  OF  SENESCENCE  IN  THE  HIGHER  FORMS 

The  process  of  senescence  in  man  and  the  higher  animals  is  not 
widely  different  in  its  general  features  from  the  age  changes  which 
occur  in  the  lower  forms  when  agamic  reproduction  is  absent.     The 


SENESCENCE  IN  HIGHER  ANIMALS  AND  MAN  271 

rate  of  metabolism  and  the  rate  of  growth  decrease,  the  water- 
content  of  the  body  Hkewise  decreases,  and  the  tissues  become 
denser.  But  the  condition  known  as  old  age  or  senility  accom- 
panied by  atrophy  of  tissues,  which  is  well  marked  in  man  and  has 
also  been  observed  in  various  mammals,  is  either  less  clearly  defined 
in  the  lower  forms  or  else  is  not  usually  reached  because  advancing 
senescence  induces  reproduction  and  rejuvenescence. 

Because  of  the  absence  of  agamic  reproduction  and  the  limited 
capacity  for  regression  and  reduction  in  these  forms,  they  consti- 
tute much  less  favorable  material  than  the  lower  forms  for  study 
and  analysis  of  age  processes,  and  theories  of  senescence  based  only 
or  chiefly  on  data  obtained  from  the  higher  forms  have  in  most 
cases  but  little  general  biological  value.  Much  of  the  literature 
of  the  subject  belongs  primarily  to  the  medical  field  and  throws 
Httle  light  upon  the  general  biological  problem  of  senescence,  but 
various  attempts  have  been  made  to  formulate  general  theories  of 
senescence  from  the  study  of  the  higher  animals  and  man  alone.' 

In  the  following  sections  of  this  chapter  the  chief  characteristics 
of  senescence  in  the  higher  forms  are  briefly  considered  and  the 
bearing  of  some  of  the  recent  experimental  work  upon  the  problem 
is  discussed. 

THE   RATE    OF   METABOLISM 

]Most  authorities  agree  that  the  rate  of  metabolism  in  man  and 
mammals,  so  far  as  determined,  undergoes  in  general  a  decrease 
with  advancing  age.^  Rubner  has  attempted  to  show  that  in  warm- 
blooded animals  the  rate  of  metabolism  per  unit  of  surface  of  the 

'  The  following  references  are  selected  from  the  more  recent  literature  dealinp 
primarily  with  senescence  and  old  age  in  man:  Bilancioni,  '11,  with  bibliograi)hy; 
Demange,  '86;  Friedmann,  '02;  Lorand,  '11,  with  bibliography;  MctchnikotI,  '03, 
'10;  Ribbert,  '08;  Rubner,  '08.  Recent  more  general  considerations  of  the  problem 
of  senescence,  but  concerned  chiefly  with  man  and  the  higher  animals,  are  Dastre,  '03; 
Muhlmann,  '00,  '10;    Minot,  '08,  '13. 

^  The  article  by  Magnus-Levy  on  "Metabolism  in  Old  .\ge"  with  bibliograiihy, 
in  the  Anglo-.\merican  issue  of  von  Xoorden's  Metabolism  and  Practical  Medicine 
(1907),  is  a  valuable  general  survey  of  our  knowledge  on  the  subject.  See  also  .Muhl- 
mann, '00  (p.  164).  .\mong  special  papers  dealing  with  the  question  of  mctalxilic 
changes  in  relation  to  age  in  man  and  mammals  may  be  mentioned  .V.  \.  and  A.  M. 
Hill,  13;  von  Hosslin,  '88;  Kovesi,  '01;  Magnus-Levy  and  I'aik.  '90;  Rubner,  '83, 
'85,  '08,  '09;   Sonden  and  Tigerstedt,  '95;   Speck,  '89. 


272 


SEXESCE^XE  AND  REJUVENESCENCE 


body  is  constant  irrespective  of  age.  Table  V  (Rubner,  '85)  gives 
the  rate  of  metabolism  in  man  at  different  ages,  measured  in  terms 
of  heat  production  in  calories  for  periods  of  twenty-four  hours, 
and  also  the  heat  production  per  kilogram  of  body-weight  and  per 
square  meter  of  body-surface. 

TABLE  V 


Weight  of  Persons  in  Experiment 
in  Kilograms 


Children 


03- 
8. 

4- 
7- 
9. 

4- 


Man  during  medium  labor  67 


Calories  in 
24  Hrs.  Minus 
Heat  of  Com- 
bustion of  Feces 


368 

966 

1,213 

1,411 

1,784 
2,106 

2,843 


Calories  per 
Kilo  in  24  Hrs. 


91 

81 

73 
59 

57 
52 
42 


•3 
•5 
■9 
•5 
•7 
.  I 

•4 


Body-Surface 

in  Square 
Centimeters 


3,013 

7,191 

7,681 

10,156 

12,122 

14,491 
20,305 


Calories  per 

Square  Meter 

of  Body-Surface 


1,221 
1,343 
1,579 
1,389 
1,472 
1,452 
1,399 


It  is  evident  from  this  table  that  the  heat  production  per  square 
meter  of  surface  does  show  a  considerable  degree  of  constancy  in 
the  individuals  of  different  sizes  and  weights.  In  various  other 
papers  Rubner  has  presented  additional  evidence  for  his  view  that 
the  rate  of  metabolism  per  unit  of  body-surface  remains  essentially 
the  same  throughout  life.  According  to  Rubner  then  the  rate  of 
metabolism  is  in  some  way  regulated  by  the  relative  amount  of 
body-surface,  i.e.,  the  loss  of  heat  determines  the  heat  production, 
and  since  the  surface  increases  less  rapidly  than  the  volume  or 
weight  of  the  body  the  rate  of  metabohsm  per  unit  of  weight  must 
decrease,  as  the  third  column  of  Table  V  shows. 

This  view  has  not  found  general  acceptance.  Not  only  has  the 
method  of  measuring  body-surface  been  criticized,  but  it  has  been 
pointed  out  that  during  later  life  in  man  the  rate  of  metabolism 
and  therefore  of  heat  production  certainly  decreases  progressively 
while  the  body-surface  remains  practically  unaltered.  According 
to  Magnus-Levy  the  minimum  metabohsm  in  old  age  may  be  as 
low  as  20  per  cent  of  the  normal,  and  various  authors  have  shown 
that  the  daily  metabolic  exchange  also  decreases.  Hill  has  recently 
shown  also  that  the  ratio  of  heat  production  to  body-surface  is  not 
constant  in  rats  of  different  size.     In  small  individuals  it  is  as  high 


SENESCENCE  IN  HIGHER  ANIMALS  AND  MAN  273 

as  one  hundred  and  forty  calories;  in  medium-sized,  ninety-nine 
calories  per  square  centimeter  of  body-surface.  In  other  words, 
the  rate  of  metabolism  is  determined  by  age,  rather  than  by  surface. 
According  to  the  data  compiled  by  Magnus-Levy  from  various 
authors,  the  amount  of  proteid  necessary  to  keep  old  persons  in 
health  is  less  than  that  necessary  in  early  life.  After  a  certain 
time  old  persons  in  general  take  less  food  than  is  necessar}-  to 
maintain  their  weight,  and  a  gradual  loss  of  weight  occurs  which 
varies  in  rate  and  amount  according  to  various  conditions.  More- 
over, the  whole  course  of  the  life  history  from  youth  to  old  age  with 
its  decrease  in  bodily  activity  and  in  rate  of  growth,  and  its  advan- 
cing differentiation  and  accumulation  of  structural  substance  points 
very  clearly  to  a  decreasing  rate  of  metabolism  per  unit  of  weight. 
It  may  also  be  noted  that  the  process  of  chemical  differentiation  of 
the  brain  of  the  white  rat  during  growth  indicates  that  the  rate 
of  metabolism  is  decreasing  during  this  period  (W.  and  M.  L. 
Koch,  '13),  and  Dr.  S.  Tashiro  kindly  permits  the  statement  from 
unpublished  data  that  in  the  horseshoe  crab,  Limuliis  polyplicmus, 
the  production  of  carbon  dioxide  per  unit  of  weight  in  the  nervous 
system  decreases  as  the  weight  of  the  nervous  system  increases; 
apparently,  the  larger  and  older  the  animal,  the  lower  the  rate  of 
carbon-dioxide  production  in  the  nervous  system. 

THE  RATE  OF  GROWTH 

The  rate  of  growth  also  shows,  in  general,  a  decrease  from  early 
stages  of  development  onward;  although  in  many  cases  periodic 
or  occasional  increases  in  rate  of  greater  or  less  magnitude  occur. 
The  decrease  in  the  rate  of  growth  during  development  in  man  and 
the  higher  vertebrates  has  been  demonstrated  beyond  all  question 
from  a  great  variety  of  data,  and  its  significance  for  the  problem  of 
senescence  has  been  so  ably  presented  by  various  authors'  that  only 
a  brief  consideration  is  necessary  at  this  time.  It  must  be  remem- 
bered that,  as  Minot  ('91)  pointed  out,  absolute  increments  of 
weight,  volume,  length,  or  any  other  component  of  growth  during 
equal  successive  periods  are  not  measures  of  the  rate  of  growth,  for 

'See  particularly  Donaldson,  '95,  the  chapters  on  growth;  Minot,  '91,  '08, 
chap,  iii,  "The  Rate  of  Growth";  Miihlmann,  '00. 


274 


SENESCENCE  AND  REJUVENESCENCE 


during  each  period  the  weight  or  other  growth  component  of  the 
body  increases.  The  rate  of  growth  is  measured  by  the  propor- 
tional or  percentage  increments  in  given  periods,  consequently  the 
rate  of  growth  may  remain  constant  or  may  even  decrease,  while 
the  absolute  increments  of  growth  become  successively  larger.  In 
fact,  the  latter  possibihty  is  realized  during  a  large 
part  of  the  growth  period  in  the  higher  vertebrates. 
Many  students  of  growth  have  failed  entirely  to 
recognize  the  fact  that  the  absolute  increment  is 
not  a  correct  measure  of  the  rate  of  growth,  and 
have  therefore  reached  incorrect  conclusions. 

The  curves  presented  in  Figs.  109  and  no 
show  the  percentage  increments  of  weight  in  boys 
and  girls  from  the  first  to  the  twenty-third  year.' 
The  very  great  decrease  in  the  annual  percentage 
increment  is  at  once  apparent.  During  the  first 
year  after  birth  the  percentage  increment  of  weight 
is  200  per  cent  in  boys  and  187  per  cent  in  girls. 
During  the  second  year  it  is  only  22  per  cent  in 
boys  and  28  per  cent  in  girls.  From  this  time  on 
it  decreases  slowly  with  slight  irregularities  and 


Per  cent 
200 

180 

160 
140 

I20  4- 

100 


80 . 


60- 


40  . 


20 


Years 


I     2     3456     7    8    9    10  II  12  13  14  15  16  17  18  19  20  21  22  23 

Fig.  109. — Curve  showing  the  decrease  in  the  rate  of  growth  in  boys  from  the 
first  to  the  twenty-third  year :  each  vertical  interval  indicated  on  the  axis  of  ordinates 
represents  20  per  cent  increment  in  weight,  each  horizontal  interval  on  the  axis  of 
abscissae  one  year.  Fom  Muhlmann's  tables  (Muhlmann,  '00)  calculated  from 
Quetelet's  data. 

with  a  distinct  but  slight  increase  at  the  age  of  puberty,  after  which 
it  falls  again.  Various  other  data  from  different  sources,  including 
statistics  on  the  increment  of  body-length,  monthly  increments  of 
weight  during  the  first  year,  decrease  in  weight  during  later  life, 
etc.,  all  show  that  in  man  the  rate  of  growth  decreases,  and  that 

'  The  curves  are  based  on  the  percentage  increments  determined  by  Muhlmann 
Coo)  from  the  statistics  in  Quetelet's  U Anthropometrie  (1835  and  1840). 


SENESCENCE  IN  HIGHER  ANIMALS  AND  M A\ 


■/:> 


as  age  advances  growth  sooner  or  later  gives  place  to  reduction. 
Data  from  the  population  of  England'  give  essentially  the  same 
results.  Minot  ('08)  also  gives  data  and  curves  from  his  own 
investigations  of  the  growth  of  guinea-pigs,  rabbits,  and  chicks 
which  likewise  show  that  the  rate  of  growth  decreases  ver>'  greatly, 

particularly  during  the  early  part  of  postem- 
bryonic  life.  Figs.  1 1 1  and  1 1 2  are  curves 
from  Minot's  data  showing  the  average  daily 
percentage  increments  in  weight  of  male  and 
female  rabbits  beginning  three  days  after  birth. 
The  abscissae  represent  number  of  days  after 
birth;  the  ordinates,  percentages.  Here  again 
it  is  evident  that  the  rate  of  growth  decreases 
with  a  few  interruptions,  at  first  very  rapidly 
and  later  more  slowly.  According  to  Donaldson 
('06)  the  curve  of  growth  of  the  white  rat  is 
very  similar  to  that  of  man,  except  that  the 
length  of  the  growth-period  is  much  shorter. 
If  the  decrease  in  the  rate  of  growth  is  in  any 

and 


Per  cent 
180  . 

160  .. 

140  .. 

120  .. 

100  .. 

80 


60  .. 


40 


20 


degree  a  measure  of  the  rate  of  senescence- 


Years 


23456789 

Fig.  1 10 — Curve  showing  the  decrease  in  the  rate  of  growth  in  girls  from  the 
first  to  the  twenty-third  year:  similar  to  Fig.  109.  From  Miihlmann's  tables  (Miihl- 
mann,  '00),  calculated  from  Quetelet's  data. 


there  can  be  little  doubt  that  it  is  one  of  the  features  of  senescence 
— Minot  is  entirely  correct  in  asserting  that  the  rate  of  senescence 
is  highest  in  youth  and  lowest  in  advanced  life. 

In  most  vertebrates,  as  well  as  in  many  invertebrates,  the  fmal 
size  of  the  individual  is  subject  to  relatively  slight  variation,  and 
the  amount  of  growth  during  development  is  within  certain  limits 

'  Figs.  38  and  39  and  Tables  II  and  III  in  Minot's  Age,  Growth  and  Death  give 
these  statistics  in  graphic  and  tabular  form  as  revised  by  Donaldson  from  Robert's 
Manual  of  Anthropometry  (1878). 


276 


SENESCENCE  AND  REJUVENESCENCE 


a  fixed  quantity.  Among  the  fishes,  amphibia,  and  reptiles  there 
are,  however,  some  forms  in  which  growth  apparently  continues 
during  at  least  most  of  the  life  of  the  animal,  although  it  is  very 
slow  in  later  stages.  Growth  is  apparently  periodic  rather  than 
continuous  in  all  these  cases,  and  its  continuance  throughout  life 
or  up  to  a  late  stage  is  probably  due  to  the  fact  that  these  animals 

undergo  partial  rejuvenescence  from  time  to 
time  during  periods  of  quiescence  or  star- 
vation, a  point  which  is  discussed  below 
(pp.  299-300).  That  the  fundamental  laws  of 
growth  are  essentially  the  same  throughout 
the  organic  world  there  is  every  reason  to 
believe.  Everywhere  apparently  the  rate  of 
growth  is  high  in  the  young  organism,  or  in 
the  young  cells  and  tissues  of  the  organism, 
and  decreases  as  development  proceeds  and 
the  rate  of  metabolism  falls.  With  adequate 
nutrition  and  under  external  conditions  which 
permit  growth,  the  rate  of  growth  appears  to 
be   in   a   general   way  dependent  upon  the 


180 


270 


Days  38182838    55       77f       106^ 

Fig.  III. — Curve  showing  the  decrease  in  rate  of  growth  in  male  rabbits  from  3 
to  270  days  after  birth:  each  vertical  interval  indicated  on  the  axis  of  ordinates  repre- 
sents I  per  cent  increment  in  weight  and  each  horizontal  interval  on  the  axis  of  abscissae 
the  length  of  time  between  successive  weighings;  during  the  first  38  days  after  birth 
weighings  were  made  every  5  days,  after  that  at  increasingly  longer  intervals.  From 
Minot's  tables  (Minot,  '08). 


rate  of  metabolism.  Discussion  of  the  conception  of  growth  as  an 
autocatalytic  reaction  which  undergoes  acceleration  in  rate  to  a 
maximum  is  postponed  to  chap.  xvi. 


NUTRITION,  GROWTH,  AND  SENESCENCE 

The  advance  during  the  last  ten  years  in  our  knowledge  of  the 
chemical  constitution  of  the  proteid  molecule,  in  which  the  work  of 


SENESCENCE  IN  HIGHER  ANIMALS  AND  .MAN 


-'// 


Kossel,  E.  Fischer,  and  Abderhalden  and  their  students  has  played 
a  very  important  part,  has  opened  up  new  fields  of  investigation. 
It  is  now  possible  to  attack  the  problem  of  nutrition  and  its  rela- 
tion to  physiological  condition,  maintenance,  development,  and 
growth,  at  least  in  the  higher  animals,  with  more  exact  and  more 
scientific  methods  than  heretofore.     Since  we  have  become  familiar 

with  the  nature  of  the  constituent  substances 
{Bausteine,  i.e.,  building  stones),  the  amino- 
acids  and  certain  other  substances,  which  go  to 
make  up  the  proteid  molecule,  and  know  more 
or  less  exactly  which  of  these  substances  are 
present  and  in  what  proportions  in  various  pro- 
teids,  we  are  able  by  feeding  animals  with 
different  proteins  or  with  one  or  another  of  the 
constituent  substances  to  learn  something  of 
the  capacities  of  the  animal  for  building  up  its 
own  specific  proteid  molecules  and  of  the  rela- 
tions of  each  of  the  various  nutritive  substances 


Days  3  8  19  2838  55        80       106^  180  270 

Fig.  112. — Curve  showing  the  decrease  in  rate  of  growth  in  female  rabbits  from 
3  to  270  days  after  birth:   the  intervals  indicated  are  the  same  as  in  Fig.  in. 
Minot's  tables  (Minot,  '08). 


From 


to  its  various  activities.  Many  difficulties  still  exist  in  connection 
with  these  investigations:  the  methods  of  isolating  the  various 
substances  in  pure  form  for  feeding  are  in  many  cases  far  from 
satisfactory,  and  it  is  often  difficult  to  devise  a  food  from  the 
isolated  substances  which  the  animal  will  eat  in  quantities  suffi- 
cient to  supply  the  necessary  energy.  Moreover,  the  complexity 
of  metabohsm  and  the  impossibility  of  following  the  various  steps 
within  the  organism  are  serious  obstacles.  Notwithstanding  all 
these  difficulties  there  can  be  no  doubt  that  this  method  of  inves- 
tigation will  throw  light  on  various  features  of  life  heretofore 
obscure.     Any  extended  discussion  of  the  results  already  attained 


278  SENESCENCE  AND  REJUVENESCENCE 

in  this  field  is  quite  beyond  the  present  purpose,  and  I  do  not 
regard  myself  as  qualified  to  undertake  it;  but  certain  points  which 
bear  more  or  less  directly  upon  the  problem  of  senescence  demand 
some  consideration. 

In  extensive  and  carefully  controlled  feeding  experiments  with 
white  rats,  Osborne  and  MendeP  have  been  able  to  show  that  cer- 
tain proteins — gliadin  from  wheat  and  rye,  hordein  from  barley — 
are  adequate  for  maintenance  of  weight  and  good  nutritive  condi- 
tion, but  not,  or  only  to  a  slight  degree,  for  growth  under  the  usual 
conditions.  But  after  male  and  female  animals  had  been  fed  during 
some  five  months  with  gliadin  as  the  only  protein,  they  were  mated, 
and  the  female  gave  birth  to  four  normal  young  which  showed 
normal  growth  as  long  as  nourished  on  the  milk  of  the  mother,  and 
only  later  when  placed  on  the  gliadin  diet  showed  retarded  growth. 
During  gestation  there  must  have  been  somewhere  a  synthesis 
of  the  specific  body-proteins  in  sufficient  quantity  to  permit  the 
normal  embryonic  development  and  growth  of  the  young.  The 
ability  of  the  body  to  synthesize  from  a  certain  diet  the  substances 
necessary  for  growth  evidently  differs  under  different  physiological 
conditions.  McCollum  has  concluded  on  the  basis  of  his  experi- 
ments that  "  the  processes  of  replacing  nitrogen  degraded  in  cellular 
metabolism  are  not  of  the  same  character  as  the  processes  of 
growth,"  and  suggests  further  that  cellular  katabolism  and  repair 
do  not  involve  the  destruction  and  reconstruction  of  an  entire  pro- 
tein molecule.  Growth,  of  course,  so  far  as  it  involves  increase 
in  amount  of  proteid  substances,  must  involve  the  construction 
of  new  molecules. 

In  an  earlier  chapter  it  was  suggested  that  growth  is  funda- 
mentally the  accumulation  of  substances  which  cannot  readily 
leave  the  cell  without  change  of  constitution  and  which  under  the 
usual  conditions  are  not  readily  or  rapidly  changed  so  as  to  become 
eliminable.  If  this  conception  is  correct,  the  further  possibility 
suggests  itself  that  tissue  breakdown  and  repair,  under  ordinary 
conditions,  in  the  higher  animals,  may  consist  largely  or  wholly,  on 

'Osborne  and  Mendel,  'iia,  'iih,  '12a,  '12b,  '12c,  '13,  '14;  Mendel,  '14.  See 
also  Hopkins,  '12;  McCollum,  '11;  Ruth  Wheeler,  '13.  Osborne  and  Mendel  give 
numerous  references  to  the  literature  of  the  subject. 


SENESCENCE  IN  HIGHER  ANIMALS  AND  MAN  279 

the  one  hand,  of  the  separation  and  breakdown  of  certain  constit- 
uent chemical  groups,  which  are  less  firmly  attached  to  the  mole- 
cule or  less  stable  than  other  parts  which  remain  as  a  more  stable 
nucleus,  and,  on  the  other,  of  the  replacement  of  the  lost  parts  of 
the  molecule  from  nutritive  substances.  In  actual  protoplasmic 
growth,  however,  the  whole  molecule,  including  the  more  as  well 
as  the  less  stable  portions,  must  be  built  up  out  of  the  Bausteirie,  or 
in  some  other  way.  Consequently  some  proteins  whose  constituent 
substances  can  supply  the  losses  due  to  tissue  breakdown  may  not 
contain  in  sufhcient  quantity  or  not  at  all  certain  components 
necessary  for  the  building  up  of  new  molecules,  but  under  excep- 
tional conditions,  as  in  the  gestation  period  in  Osborne  and  Mendel's 
rats,  the  organism  may  be  able  to  synthesize  these  molecules  in 
other  ways.  The  general  relation  between  the  rate  of  growth  and 
the  rate  of  metabohsm  suggests  that  the  synthesis  of  the  more 
stable  molecules  or  molecular  groups  occurs  more  readily  with  a 
high  than  with  a  low  rate  of  metabolic  reaction,  and  this  suggestion 
is  also  in  accord  with  the  fact  that  growth,  morphogenesis,  and 
differentiation  occur  chiefly  in  the  earlier  stages  of  the  life  history. 

The  rats  fed  on  gliadin  with  maintenance  of  weight  but  little  or 
no  growth  retain  their  capacity  for  growth  for  at  least  several 
months  and,  when  placed  on  a  mixed  diet,  or  one  containing  ade- 
quate proteins,  resume  growth  at  the  normal  rate.  But  the  experi- 
ments do  not  as  yet  show  whether  they  will  retain  indefinitely  the 
capacity  for  growth.  Besides  remaining  young  as  regards  growth 
capacity,  these  animals  also  retain  the  general  appearance  of 
growing  animals  of  the  same  size.  Apparently,  progressive  develop- 
ment and  with  it  senescence  have  been  inhibited  or  greatly  retarded. 
Nevertheless,  after  long  periods  of  such  feeding  the  nervous  system 
shows  the  water-content  characteristic  of  old  animals  and  the  pos- 
sibility cannot  be  ignored  that,  even  in  the  absence  of  growth, 
progressive  changes  in  the  direction  of  greater  stability  of  the 
protoplasmic  substratum  may  have  occurred. 

The  results  of  experiments  on  mammals  with  a  diet  which  is 
adequate  qualitatively,  but  sufficient  in  quantity  only  for  main- 
tenance and  not  for  growth,  are  quite  different  from  those  of 
Osborne   and   Mendel.     Waters    ('08,    '09)    found   that   underfed 


28o  SENESCENCE  AND  REJUVENESCENCE 

cattle  might  remain  for  a  long  period  at  a  constant  body-weight 
but  at  the  same  time  undergo  an  increase  in  height  and  a  decrease 
in  the  amount  of  fat.  Evidently  the  skeleton  undergoes  growth, 
at  least  in  length  of  bones,  even  under  these  conditions,  and  other 
parts  must  grow  to  some  extent  and  in  certain  dimensions  in 
accordance  with  the  growth  of  the  skeleton,  but  this  growth  is  in 
part  at  the  expense  of  the  reserves.  After  a  certain  length  of  time 
this  growth  ceases. 

Aron  ('ii),  working  with  growing  dogs,  succeeded  in  maintain- 
ing a  constant  body-weight  for  a  long  time,  in  some  cases  nearly  a 
year,  by  limiting  the  quantity  of  food.  He  also  found  that  the 
animals  increased  in  size,  the  skeleton  underwent  growth,  and  the 
brain  retained  its  weight  or  increased  in  weight,  while  the  animals 
became  progessively  thinner  and  their  fat  reserves  and  muscular 
tissue  suffered  marked  losses.  If  the  food  was  not  increased  in 
amount  the  animals  finally  died  of  starvation  after  three  to  five 
months,  with  a  slight  loss  of  weight.  But  if  the  quantity  of  food 
was  somewhat  increased  they  could  still  be  maintained  at  a  con- 
stant weight  and  in  a  condition  of  extreme  emaciation,  but  now  no 
further  growth  occurred.  The  results  of  later  experiments  on  rats 
(Aron,  'i2,  '13)  are  essentially  similar  and  these  experiments  on 
animals  agree  well  with  the  observations  of  various  earlier  authors 
on  children. 

Aron  concludes  from  his  experiments  that  the  internal  growth- 
impulse  exists  primarily  in  the  skeleton  and  that  other  parts  merely 
follow  the  growth  of  the  skeleton  as  far  as  nutritive  conditions 
permit.  This  is  probably  true  for  mammals  or  for  vertebrates  as 
regards  growth  in  stature  during  later  stages  of  development,  but 
it  is  certainly  not  true  for  the  early  stages  of  development  of  verte- 
brates nor  for  many  invertebrates  where  no  skeleton  is  present. 
It  seems  probable  that  in  these  animals  growth  of  the  more  stable 
substances  of  the  body,  in  part  at  the  expense  of  the  less  stable,  has 
occurred.  The  diet  in  these  cases  is  merely  quantitatively,  not 
qualitatively  insufficient;  it  contains  the  constituents  necessary 
for  the  construction  of  the  relatively  stable  structural  substances, 
but  not  in  sufficient  quantity  for  the  growth  of  all  parts.  Under 
these  conditions  it  might  be  expected  that  growth  or  maintenance, 


SENESCENCE  IN  HIGHER  ANIMALS  AND  MAN  281 

if  it  occurs  anywhere,  would  be  limited  to  the  more  stable  tissues  or 
substances  of  the  body,  while  the  less  stable  would  undergo  more 
or  less  reduction,  for  in  the  one  case  the  losses  from  breakdown  are 
slight  and  are  more  than  balanced,  while  in  the  other  they  are 
greater  and  are  not  balanced  and  the  products  of  breakdown  of 
the  less  stable  tissues  take  part  to  a  greater  or  less  extent  in  the 
upbuilding  of  the  more  stable.  The  organic  structural  substance 
of  the  skeleton  is  scarcely  to  be  regarded  as  living;  it  is  rather  of 
the  nature  of  a  secretion,  and  after  its  formation  it  takes  but  little 
part  in  metabolism,  except  when  altered  functional  conditions 
determine  a  change  in  bone  structure.  Consequently  in  underfed 
animals  there  is  little  loss  of  skeletal  substance,  and  every  addition 
counts  for  growth.  Skeletal  growth  may  therefore  continue  while 
reduction  is  going  on  in  various  other  organs,  the  products  of 
breakdown  of  the  latter  serving  to  build  up  the  more  stable  sub- 
stance of  the  former. 

As  regards  the  nervous  system,  conditions  are  somewhat 
similar.  The  nervous  system  is  certainly  one  of  the  most  stable, 
perhaps  the  most  stable  living  tissue  in  the  body.  Its  cells  persist 
throughout  life,  and  dedifferentiation  of  nerve  cells  is  not  known  to 
occur  in  vertebrates.  The  losses  of  the  nervous  system  during 
starvation  are  relatively  slight,  and  in  underfed  animals  it  main- 
tains its  weight  or  grows  at  the  expense  of  the  less  stable  tissue, 
as  the  products  of  their  breakdown  are  synthesized  into  more 
stable  forms  in  the  nervous  system,  and  so  become  more  permanent 
constituents  of  the  structural  substratum  of  the  bod>'.  This 
stability  of  the  nervous  system  is  not,  however,  like  that  of  the 
skeleton,  the  stability  of  a  dead  secretory  substance,  but  is  the 
stability  of  a  living  protoplasm  and  is  undoubtedly  associated  with 
the  high  metabolic  rate  in  the  nervous  system. 

The  result  of  return  to  a  normal  diet  after  a  period  of  insufiicient 
nutrition  apparently  depends  in  part  on  the  length  of  that  period. 
It  has  been  clearly  demonstrated  that  in  man  as  well  as  in  animals 
the  retarding  effect  upon  growth  of  even  a  considerable  period  of 
insuflfiicient  nutrition  may  be  compensated  later  on  a  normal  diet. 
But  it  is  also  true  that  a  sufficiently  long  period  of  underfeeding 
may  result  in  permanent  "stunting,"  the  body  apparently  being 


282  SENESCENCE  AND  REJUVENESCENCE 

unable  to  recover  its  full  capacity  for  growth.  Stunting  in  man  and 
the  mammals  is  undoubtedly  due  in  large  measure  to  subnormal 
skeletal  growth,  and  while  the  effect  of  long-continued  underfeeding 
on  the  physiological  condition  of  the  skeletal  tissues  is  not  known, 
the  facts  suggest  that  the  usual  relation  between  senescence  and 
growth  is  altered.  In  other  words,  the  cells  which  give  rise  to  the 
skeletal  substance  probably  undergo  some  degree  of  senescence 
during  underfeeding  without  being  able  to  produce  as  much  skeletal 
substance  as  under  continuous  good  nutritive  conditions,  conse- 
quently their  rate  of  metabolism  is  lower  and  they  are  less  capable 
of  producing  skeletal  substance  after  such  a  period  than  the  cells 
of  an  individual  of  the  same  size  which  has  been  continuously  well 
fed.  The  skeleton  of  the  individual  which  has  been  subjected 
to  underfeeding  for  a  sufficiently  long  time  will  therefore  cease  to 
grow,  even  under  good  nutritive  conditions,  at  a  smaller  size  than 
that  of  the  continuously  well-fed  individual,  and  very  probably 
the  same  is  true  to  a  greater  or  less  extent  in  other  tissues.  In  the 
underfed  animal  the  proportion  of  more  stable  to  less  stable  com- 
ponents of  the  tissues  must  increase  more  rapidly  than  where  nutri- 
tion is  sufficient  for  all  requirements,  for  in  the  former  case  the  less 
stable  components  must  break  down  to  a  larger  extent  than  in  the 
latter.  In  the  absence  of  sufficient  food  these  substances  must 
serve  to  a  larger  extent  as  a  source  of  energy  or  for  the  synthesis 
of  the  more  stable  components  than  where  sufficient  nutritive  sub- 
stance is  available.  Consequently  the  substitution  of  more  stable 
for  less  stable  substances  in  the  tissues  goes  on  during  the  period 
of  underfeeding,  but  with  less  than  the  usual  amount  of  growth 
because  the  less  stable  substances  are  present  as  structural  com- 
ponents in  smaller  proportion  than  under  the  usual  conditions. 
After  a  long  period  of  underfeeding  the  tissues  are  physiologically 
older  and  therefore  less  capable  of  growth,  even  when  nutrition 
is  present  in  excess,  than  in  the  continuously  well-fed  animal  of  the 
same  size.  According  to  this  conception,  senescence  in  the  higher 
animals  and  man  may  proceed  to  some  extent  even  when  httle  or 
no  growth  occurs,  because  the  body  substance  is  gradually  trans- 
formed to  a  greater  or  less  extent  from  more  active  to  more  stable 
conditions. 


SENESCENCE  IN  HIGHER  ANIMALS  AND  MAN  283 

CHANGES  IN  WATER-CONTENT  AND  CHEMICAL  CONSTITUTION 

From  a  certain  stage  of  development  on,  the  water-content  of 
the  body  undergoes  in  general  a  decrease  with  advancing  age,  as 
many  authors  have  shown.  Davenport  ('97)  has  found  that  in 
the  frog  the  percentage  of  water  increases  from  56  to  96  per  cent 
during  the  first  two  or  three  weeks  after  hatching,  and  then  begins 
to  decrease.  In  the  chick  embryo  and  the  human  fetus  the  per- 
centage of  water  decreases  from  an  early  stage.  Aron  ('13)  has 
compiled  the  data  concerning  the  changes  in  water-content  in  man 
and  the  higher  animals. 

The  decrease  in  water-content  is  not  uniform  for  the  difYerent 
organs,  nor  is  its  progress  in  a  given  organ  entirely  uniform  in  all 
cases.  The  extensive  investigations  of  Donaldson  and  Hatai'  on 
the  water-content  of  the  nervous  system  of  the  white  rat  show 
that  the  percentage  of  water  in  this  tissue  changes  very  regularly 
with  advancing  age.  At  birth  it  is  about  88  per  cent,  at  maturity 
78  per  cent,  and  it  is  altered  only  very  slightly  by  nutritive  con- 
ditions and  external  factors.  Donaldson  states  that  it  afifords  the 
best  index  known  of  the  age  of  these  animals.  It  is  probable  that 
further  investigations  on  other  mammals  would  give  similar  results 
for  the  nervous  system,  but  for  various  other  tissues,  e.g.,  the 
muscles,  the  variation  in  water-content  is  much  greater. 

It  is  an  undoubted  fact  that  after  a  certain  stage  the  body 
becomes  more  and  more  solid  as  the  structural  substance  accumu- 
lates. The  decreasing  water-content  is  in  fact  probably  to  some 
extent  merely  another  aspect  of  the  process  of  structural  accumula- 
tion in  the  cells,  although  it  may  be  in  part  the  result  of  changes  in 
the  aggregate  condition  of  the  colloids,  as  Bechhold  ('12)  and  others 
have  suggested. 

It  is  impossible  to  consider  at  length  the  changes  in  chemical 
constitution  which  occur  with  advancing  age.  Aron's  recent  com- 
pilation of  the  data  on  the  biochemistry  of  growth  ('13)  affords  a 
good  survey  of  our  present  knowledge  on  this  question.  In  general 
an  increase  in  the  percentage  of  proteid  and  of  inorganic  substances 
occurs,  and  this  increase  is  more  rapid  during  the  earlier  >-ears  of 

'  Hatai, '04;  Donaldson, 'iia, 'iii;  Donaldson  and  Hatai, '11. 


284  SENESCENCE  AND  REJUVENESCENCE 

life  than  later.  Certain  organs  also  undergo  characteristic  changes 
in  constitution,  but  the  relation  between  these  changes  and  the  age 
cycle  is  in  most  cases  not  yet  clear. 

THE  MORPHOLOGICAL  CHANGES 

If  senescence  is  merely  one  aspect  of  progressive  development 
the  morphology  of  senescence  in  man  and  the  higher  forms  is  simply, 
as  elsewhere,  the  morphology  of  progressive  development.  The 
morphological  changes  in  the  cells  consist  in  general  of  the  appear- 
ance of  more  or  less  definite  structural  substances,  which  differ  in 
form  and  character  according  to  the  direction  of  differentiation  in 
particular  cells  or  organs.  Morphological  differentiation  of  the 
cell  involves  either  an  accumulation  in  the  cytoplasm  of  substances 
different  in  appearance  and  constitution  from  the  cytoplasmic  sub- 
stratum of  the  embryonic  cell,  or  a  replacement  of  the  embryonic 
substratum  by  such  substances.  This  process  of  differentiation, 
or  cytomorphosis  as  Minot  prefers  to  call  it,  very  commonly  involves 
an  increase  in  the  volume  of  the  cytoplasmic  portions  of  the  cell 
as  compared  with  the  nucleus.  In  embryonic  cells  the  nucleus  is  in 
general,  relatively  to  the  cytoplasm,  larger  than  in  differentiated 
cells.  Alinot  has  laid  particular  emphasis  on  this  change  in  the 
proportion  of  nucleus  and  cytoplasm  as  a  fundamental  feature  of 
progressive  development  and  as  the  determining  factor  in  the 
decrease  in  metabolic  rate  which  occurs  in  senescence.  Such  a 
change  undoubtedly  does  occur  in  at  least  many  cells  in  the  course 
of  dift'erentiation,  particularly  in  the  higher  animals,  but  it  is  by 
no  means  universal,  as  Minot  maintains.  In  certain  of  the  lower 
animals  there  is  little  if  any  difference  between  the  embryo  and 
the  adult  in  this  respect,  and  the  differentiation  of  plant  cells  is 
very  generally  accompanied  by  vacuolization  rather  than  by  in- 
crease of  cytoplasm. 

Figs.  113  and  114  show  embryonic  and  differentiated  cells  from 
the  spinal  cord  of  the  chick.  The  cells  in  Fig.  113  are  from  the 
neural  tube  soon  after  its  formation,  and  in  Fig.  114,  drawn  to 
the  same  scale,  nerve  cells  from  the  spinal  cord  after  eleven  days 
of  incubation,  at  which  time  some  of  the  nerve  cells  have  attained 
practically  their  full  size.     Measurements  of  the  volume  of  nuclei 


SENESCENCE  IN  HIGHER  ANLMALS  AND  MAX 


28: 


and  cell  bodies  indicate  that  there  is  comparative!}'  Hlllc  change 
in  proportion  during  the  process  of  differentiation.  (Jf  course 
such  measurements  are  not  exact,  and,  besides,  the  measurements  of 
the  cytoplasm  do  not  include  the  dendrites  and  the  nerve  fiber 
arising  from  the  cell:  if  the  volume  of  these  were  added  to  the 
cytoplasmic  volume  of  the  cell  the  total  would  undoubtedly  show 


113 


114 


/V'''-',')v  V  ^»VC: '.• '.".\V' 

^;^^'^'l^y:'^;:.0'^^'!•■  .'•''.■:'.'.'.,•■ 


Figs.  113,  114. — Cells  from  the  nervous  system  of  the  chick  embryo:  I-'ig.  113, 
embryonic  cells  from  neural  tube  at  31  hours;  Fig.  114,  dilTerentiatcd  motor 
cells  from  spinal  cord  at  11  days,  drawn  to  the  same  scale.  From  embryological 
preparations  of  the  University  of  Chicago. 

an  increase  in  cytoplasmic  volume  during  ditTerentiation.  But 
how  can  the  dendrites  and  the  nerve  fiber  contribute  to  decrease  the 
rate  of  metabolism  in  the  cell  body,  since  they  are  merely  slender 
outgrowths  from  it  ?  The  cell  body  has  unquestionably  undergone 
senescence  during  differentiation,  l)ut  without  any  very  great 
change  in  the  nucleo-cytoplasmic  relation.     A  marked  proportional 


286  SENESCENCE  AND  REJUVENESCENCE 

increase  in  the  amount  of  cytoplasm  does  occur  in  many  cases,  but 
it  is  an  incidental  rather  than  a  fundamental  feature  of  senescence. 
The  important  change  is  not  the  change  in  amount,  but  the  change 
in  the  proportion  of  chemically  active  to  inactive,  or  more  active 
to  less  active  substance. 

In  the  higher  animals  and  man  morphological  differentiation 
of  the  cells  is  much  more  conspicuous  and  varied  than  in  the  lower 
forms,  but  the  essential  nature  of  the  process  is  evidently  the  same 
in  all  forms.  Differentiation  consists  primarily,  not  in  increase  in 
amount  of  cytoplasm,  but  in  the  accumulation  of  substances  differ- 
ent in  some  way  from  the  embryonic  cytoplasm  and  giving  the  cell 
its  characteristic  structure.  And  it  is  unquestionably  the  increase 
in  these  substances,  not  the  increase  in  the  amount  of  cytoplasm, 
which  determines  the  decrease  in  rate  of  metabolism  and  rate  of 
growth.  The  structural  substances  produced  by  different  cells 
differ  in  character  in  one  way  or  another  because  in  the  course 
of  development  different  metabolic  conditions  arise  in  different 
regions,  and  in  the  higher  animals  these  conditions  must  be  more 
definite  and  fixed  in  character  than  in  the  lower  organisms,  because 
the  degree  of  individuation  is  higher,  i.e.,  the  correlation  between 
parts  is  more  intimate  and  definite.  These  factors,  together  with 
the  limited  regressibility  in  many  parts,  must  also  determine  that 
differentiation  shall  proceed  farther  than  in  the  lower  forms.  The 
structural  differences  in  different  cells  are  more  permanent  and  more 
conspicuous  and  in  general  involve  the  cell  to  a  greater  extent. 

So  far  as  they  have  turned  their  attention  to  the  phenomena  of 
senescence  the  anatomists,  histologists,  and  pathologists  have 
often  failed  to  recognize  what  the  study  of  the  lower  organisms 
forces  us  to  admit  as  a  fact,  viz.,  that  senescence  is  merely  one  aspect 
of  development,  and  have  confined  their  attention  to,  and  based 
their  theories  upon,  the  morphological  changes  which  occur  in  later 
life,  and  particularly  in  what  we  are  accustomed  to  call  old  age. 
One  reason  for  this  attitude  among  those  investigators  who  have 
been  chiefly  concerned  with  man  lies  in  the  fact  that  old  age  in 
man  and  the  higher  vertebrates  is  associated  with  certain  morpho- 
logical changes  in  the  cells  which  seem  to  be  different  in  character 
and  direction  from  the  developmental  changes.     These  changes 


SENESCENCE  IN  HIGHER  ANIMALS  AND  MAN  287 

are  commonly  known  as  senile  atrophy.'  They  consist  essenlially 
of  a  decrease  in  size,  with  more  or  less  degeneration  of  cells.  These 
changes  are  often  so  extensive  and  so  widely  distributed  that  there 
is  considerable  decrease  in  size  and  weight  of  the  body  as  a  whole. 

The  atrophy  may  involve  to  a  greater  or  less  extent  most  or  all 
of  the  more  highly  specialized  organs  of  the  body,  liver,  kidneys, 
alimentary  tract,  lungs,  muscular  system,  skeleton,  and  nervous 
system.  The  arterial  system  always  shows  changes  in  the  direc- 
tion of  decreased  elasticity  and  contractility,  and  the  hardening 
of  the  walls  known  as  arteriosclerosis  is  very  commonly  present, 
although  some  authors  maintain  that  it  is  not  a  characteristic 
feature  of  old  age.  The  heart  often  becomes  h>pertrophied  in- 
stead of  atrophied,  but  this  is  believed  by  many  to  be  a  functional 
reaction  to  the  increased  work  of  the  heart  in  consequence  of  the 
changes  in  the  arterial  system,  rather  than  a  feature  of  old  age. 
The  connective  tissue  becomes  stiffer  and  harder,  but  its  less 
highly  specialized  forms  may  increase  and  take  the  place  of  more 
highly  specialized  organs  or  tissues  which  have  undergone  atroph}-. 
In  connection  with  these  changes  of  old  age  the  deposition  of  fatty 
substances,  evidently  products  of  metabolism,  occurs  in  the  cells 
of  muscles,  liver,  brain,  and  various  other  tissues. 

The  difference  in  appearance  of  the  spinal  ganglion  cells  of  man 
at  birth  and  in  a  case  of  death  from  old  age  at  ninety-two  years  are 
shown  in  Figs.  115  and  116.  In  the  first  figure  the  young  cells 
have  not  yet  attained  their  full  size,  but  compared  with  them,  the 
cells  on  the  left  of  the  second  figure  are  seen  by  the  spaces  about 
them  to  be  greatly  shrunken  and  their  cytoplasm  contains  numerous 
fat  granules  stained  black  by  the  method  of  preparation.  On  the 
right  of  Fig.  116  the  debris  of  two  cells  which  have  undergone 
degeneration  is  seen. 

The  atrophy  of  tissues  in  old  age  is  manifestly  associated  with 
the  decrease  in  rate  of  metabolism.  It  is  a  well-known  fact  that  a 
decrease  or  cessation  of  functional  activity  in  the  specialized  organs 
after  their  development  brings  about  atrophy  quite  independently 

'  For  more  recent  discussions  of  senile  atro[)hy  see  Bilancioni,  '11;  DemanRC,  '86; 
Metchnikoff, '03, '10;  Minot, '08,  chap,  ii;  Miihlmann, '00, '10;  Ribbert, '08;  articles 
in  medical  dictionaries,  cyclopedias,  etc. 


288 


SENESCENCE  AND  REJUVENESCENCE 


of  age.  Under  such  conditions,  or  where  the  rate  of  metabolism 
has  fallen  below  a  certain  level  in  consequence  of  age,  the  break- 
down and  elimination  of  the  substratum  is  not  compensated  by  the 
synthesis  of  new  substance,  consequently  a  decrease  in  size  and 
finally  cell  death  occur.  Atrophy,  in  the  higher  animals  differs 
from  reduction  in  the  lower  forms  in  that,  while  decrease  in  size 
occurs,  there  is  little  or  no  dedifferentiation.  The  cell  has  appar- 
ently become  so  highly  differentiated  that  it  has  lost  the  capacity 
for  synthesizing  a  substratum  adequate  in  quantity  or  constitution 


3^ 


116 


Figs.  115,  116. — Cells  from  the  first  cer\dcal  ganglion  of  man  at  different  ages: 
Fig.  lis,  from  fetus  killed  by  accident  of  birth;  Fig.  116,  from  man  dying  of  old  age 
at  ninety-two  years,  showing  on  the  left  two  cells  shrunken  and  undergoing  atrophy 
and  on  the  right  the  outlines  of  spaces  formerly  occupied  by  cells  now  degenerated. 
After  Hodge,  '94. 

to  carry  on  metabolism.  Consequently  the  losses  from  degradation 
and  breakdown  of  the  existing  substratum  are  not  compensated  by 
the  synthesis  of  new  substratal  substance,  and  sooner  or  later  the 
fundamental  mechanism  of  the  cell  is  destroyed  and  degeneration 
and  death  occur.  The  atrophy  of  old  age  in  organs  of  such  funda- 
mental importance  as  the  nervous  system  indicates  that  there  is 
some  truth  in  the  statement,  so  often  made,  that  the  later  stages  of 
senescence  are  a  "wearing  out"  of  the  physiological  mechanism  or 
some  essential  part  of  it.  Apparently  the  nerve  cells  or  some  of 
them  do  "wear  out"  because  they  are  no  longer  able  to  synthesize 


SENESCENCE  IX  HIGHER  ANIMALS  AND  MAN  289 

the  substratum  necessary  for  their  continued  function.  But  even 
though  the  final  stage  of  senescence,  which  terminates  in  death, 
may  be  regarded  as  a  wearing  out  and  a  breaking  down  of  the 
physiological  mechanism  at  some  point,  it  must  not  be  forgotten 
that  this  stage  is  merely  the  final  stage  of  progressive  development 
and  that  the  factors  which  determine  it  act  from  the  beginning  of 
development  on. 

CONCLUSION 

So  far  as  the  facts  go,  the  process  of  senescence  appears  to  be 
essentially  the  same  in  the  higher  and  lower  organisms;  the  chief 
difference  is  that  with  the  absence  of  reproduction  and  the  greater 
degree  of  individuation  and  differentiation  the  later  atrophic  stages 
of  senescence  are  conspicuous  and  characteristic  features  of  the 
life  history  in  the  higher  forms,  while  in  the  lower  they  either  do 
not  appear  or  else  occur  in  only  a  few  cells  at  any  given  time.  From 
the  lowest  forms  to  man  senescence  is  simply  one  aspect  of  the 
developmental  process,  and  we  may  expect  to  find  it  occurring 
wherever  the  progressive  changes  are  not  balanced  or  overbalanced 
by  regression. 

The  apparent  continuity  and  irregressibility  of  senescence  in 
man  and  the  higher  forms  is  responsible  for  the  very  general  belief 
that  the  process  is  irregressible  everywhere,  but  the  plants  and  lower 
animals  show  us  clearly  enough  that  this  is  not  the  case.  Viewed  in 
the  light  of  what  we  have  learned  from  the  lower  forms,  senescence 
in  the  higher  animals  and  man  is  merely  a  less  frequently  inter- 
rupted process  of  the  same  kind  as  that  which  occurs  in  all  pro- 
gressive stages  of  the  Hfe  cycle  in  the  plants  and  the  lower  animals. 

REFERENCES 

Aron,  H. 

191 1.  "Wachstum  und  Emahrung,"  Biochem.  Zcilschr.,  XXX. 

1912.  "Weitere  Untersuchungen  iiber  die  Beeinflussung  des  Wachstums 
durch  die  Emahrung,"  Verhandlungcn  d.  Gcscll.  f.  Kindcrhcil- 
kundc. 

1913.  Biochemie  des  Wachstums.  Erweiterte  Sonderausgabe  aus  dem 
Haiuibuch  d.  Biochemie.     Ergiinzungsbd.     Jena. 

Bechhold,  H. 

191 2.     Die  Kolloide  in  Biologic  und  Mcdezin.     Dresden. 


2 go  SENESCENCE  AND  REJUVENESCENCE 

BiLANCIONI,  G. 

igii.  "II  problema  della  vecchiaia  e  della  morte  naturale,"  Arch,  di 
Farmacol.  sperimentale,  XL 

Dastre,  a. 

1903.  La  vie  et  la  mart.     Paris. 

Davenport,  C.  B. 

1897.  "The  Role  of  Water  in  Growth,"  Proc.  of  the  Boston  Soc.  of  Nat. 
Hist.,  XXVIII. 

Demange. 

1886.     Etude  dinique  et  anatomo-pathologiqiie  de  la  vieillesse. 

Donaldson,  H.  H. 

1895.     The  Growth  of  the  Brain.     London. 

1906.     "A  Comparison  of  the  White  Rat  with  Man  in  Respect  to  Growth 

of  the  Entire  Body,"  Boas  Memorial  Volume.    New  York. 
1911a.  President's  Address;    Philadelphia  Neurological  Society.    Jour. 

of  Nerv.  and  Mental  Diseases,  XXXVIII. 
igiib.  "The  Effect  of  Underfeeding  on  the  Percentage  of  Water,  on  the 

Ether-Alcohol  Extract  and  on  Medullation  in  the  Central  Nervous 

System  of  the  Albino  Rat,"  Jour,  of  Comp.  Neurol.,  XXI. 

Donaldson,  H.  H.,  and  Hatai,  S. 

191 1.  "A  Comparison  of  the  Norway  Rat  with  the  Albino  Rat  in  Respect 
to  Body  Length,  Brain  Weight  and  the  Percentage  of  Water  in 
Both  the  Brain  and  the  Spinal  Cord,"  Jour,  of  Comp.  Neurol.,  XXI. 

Friedmann,  F. 

1902.     Die  Altersverdnderungen  mid  ihre  Behandlung.     Wien. 

Hatai,  S. 

1904.  "The  Efifect  of  Partial  Starvation  on  the  Brain  of  the  White  Rat," 
Am.  Jour,  of  Physiol.,  XII. 

Hill,  A.  V.  and  A.  M. 

1913.  "  Calorimetrical  Experiments  on  Warmblooded  Animals,"  Jour,  of 
Physiol,  XLVI. 

Hodge,  C.  F. 

1894.  "Changes  in  Ganglion  Cells  from  Birth  to  Senile  Death,"  Jour, 
of  Physiol.,  XVII. 

Hopkins,  F.  G. 

1912.  "Feeding  Experiments  Illustrating  the  Importance  of  Accessory 
Factors  in  Normal  Dietaries,"  Jour,  of  Physiol.,  XLIV. 

Hosslin,  H.  von. 

1888.  "  Uber  die  Ursachen  der  scheinbaren  Abhangigkeit  des  Umsatzes 
von  der  Grosse  der  Korperoberflache,"  Arch.f.  Physiol.,  Jhg.  1888. 


SENESCENCE  IN  HIGHER  ANIMALS  AND  MAN  291 

Koch,  W.  and  M.  L. 

1913.  "Contributions  to  the  Chemical  Differentiation  of  the  Central 
Nervous  System:  III,  The  Chemical  Differentiation  of  the  Brain 
of  the  Albino  Rat  during  Growth,"  Jour,  of  Biol.  Chem.,  XV. 

KovESi,  G. 

1901.  "tJber  den  Eiweissumsatz  im  Greisenalter,"  Zcntralbl.  /.  inncre 
Med.,  XXII. 

LORAND,  A. 

191 1.     Das  Altern,  seine  Ursachen  mid  seine  Behandlung.     Leipzig. 
MCCOLLUM,   E.   V. 

1911.  "The  Nature  of  the  Repair  Processes  in  Protein  Metabolism," 
Am.  Jour,  of  Physiol.,  XXIX. 

Magnus-Levy,  A.,  and  Falk,  E. 

1899.  "Der  Lungengaswechsel  des  IVIenschen  in  den  verschiedenen 
Altersstufen,"  Arch.  f.  Physiol.     Supplement-Band. 

Marchal,  p. 

1904.     Recherches  sur  la  biologie  et  le  developpcment  des  Hymenopteres: 

I,   La   polyembryonie   ou   germinogonie,"   Arch,    de   zool.    Exp., 

(4)  II. 
Mendel,  L.  B. 

1914.  "Viewpoints  in  the  Study  of  Growth,"  Biochem.  Bull.,  III. 

Metschnikoff,  E. 

1903.     The  Nature  of  Man.    English  translation:  New  York  and  London. 
1910.     The  Prolongation  of  Life.     English  translation:    New  York  and 
London. 

MiNOT,  C.  S. 

1891.     "Senescence  and  Rejuvenation,"  Jour,  of  Physiol.,  XII. 
1908.     The  Problem  of  Age,  Growth  and  Death.     New  York. 
1913.     Moderne  Probleme  der  Biologie.     Jena. 

MUHLMANN,  M. 

1900.  Uber  die  Ursachc  des  Alters.     Wiesbaden. 

1910.  "Das  Altern  und  der  physiologische  Tod,"  Sanimluiig  aiiat.  u. 
physiol.  Vorlr.,  XI. 

Osborne,  T.  B.,  and  Mendel,  L.  B. 

191  ic.  "Feeding  Experiments  with  Isolated  Food-Substances,"  Parts  I 
and  II.     Carnegie  Inst.,  Publ.  156. 

igiib.  "The  Role  of  Different  Proteins  in  Nutrition  and  Growth,"  Sci- 
ence, XXXIV. 

1912a.  "Beobachtungen  iiber  Wachstum  bei  Futterungsversuchcn  mit 
isolierten  Nahrungssubstanzen,"Ze//5c//r./.  physiol.  Chem..  LXXX. 

19126.  "The  Role  of  Gliadin  in  Nutrition,"  Jour,  of  Biol.  Chem.,  XII. 


292  SENESCENCE  AND  REJUVENESCENCE 

Osborne,  T.  B.,  and  Mendel,  L.  B. 

1912c.   "Maintenance   Experiments   with    Isolated    Proteins,"   Jour,    of 
Biol.  Chem.,  XIII. 

1913.  "The  Relation  of  Growth  to  the  Chemical  Constituents  of  the 
Diet,"  Jour,  of  Biol.  Chem.,  XV. 

1914.  "Amino-Acids  in  Nutrition  and  Growth,"  Jour,  of  Biol.  Chem., 
XVII. 

Patterson,  J.  T. 

1913.  " Polyembryonic  Development  in  Tatusia  novetncincta,"  Jour,  of 
Morphol.,  XXIV. 

RiBBERT,  H. 

1908.     Der  Tod  aus  AUersschwdche.     Bonn. 

RUBNER,  M. 

1883.     "liber  den  Einfluss  der  Korpergrosse  auf  Stoff-  und  Kraftwechsel," 

Zeitschr.  f.  Biol.,  XIX. 
1885.     " Calorimetrische  Untersuchungen,"  Zeitschr.  f.  Biol.,  XXI. 

1908.  Das  Problem  der  Lebensdauer  und  seine  Beziehungen  zu  Wachstum 
und  Erndhrung.     Miinchen. 

1909.  Kraft  und  Stof  im  Haushalte  der  Natur.    Leipzig. 

SiLVESTRI,  F. 

1906.  "Contribuzione  alia  conoscenza  biologica  degli  Imenotteri  parasiti: 
I,  Biologia  del  Litomastix  truncatellus,'"  Ann.  Scuola  Agric.  Por- 
tici,  VI. 

SONDEN,  K.,  und  TiGERSTEDT,  R. 

1895.  "Untersuchungen  iiber  die  Respiration  und  den  Gesammtstoff- 
wechsel  des  Menschen,"  Skand.  Arch.f.  Physiol.,  VI. 

Speck,  C. 

1889.  "Das  normale  Athmen  des  Menschen,"  Schriften  d.  Gesell.  z. 
Beford.  d.  ges.  Wissensch.,  XII. 

Waters,  H.  J. 

1908.  "The  Capacity  of  Animals  to  Grow  under  Adverse  Conditions," 
Proc.  of  the  Soc.for  the  Promotion  of  Agric.  Sci.,  XXIX. 

1909.  "The  Influence  of  Nutrition  upon  the  Animal  Form,"  Proc.  of 
the  Soc.for  the  Promotion  of  Agric.  Sci.,  XXX. 

Wheeler,  Ruth. 

1913.     "Feeding  Experiments  with  Mice,"  Jour,  of  E.xp.  Zool.,  XV. 

Wilder,  H.  H. 

1904.     "Duplicate  Twins  and  Double  Monsters,"  Am.  Jour,  of  Anat.,  III. 


CHAPTER  XII 

REJUVENESCENCE  AND  DEATH  IN  THE  HIGHER  ANIMALS 

AND  MAN 

REJUVENESCENCE   IN   THE    LIFE    HISTORY 

While  much  has  been  written  concerning  senescence  and  death 
in  man  and  the  higher  animals,  but  little  attention  has  been  paid 
to  the  question  of  the  occurrence  of  rejuvenescence,  and  many 
authorities  still  maintain  that  life  is  always  a  progressive  process 
and  that  rejuvenescence  does  not  occur.  It  is  of  course  true  that 
in  the  higher  animals  the  progressive  features  of  development  are 
predominant  and  that  development  ends  in  death,  and  many 
studies  of  senescence  have  been  based  on  these  forms  alone,  without 
consideration  or  knowledge  of  the  lower  organisms.  But- if  we  are 
to  reach  a  general  conception  of  the  age  cycle  in  organisms,  the  wide 
occurrence  and  significance  of  dedififerentiation  and  rejuvenescence 
in  the  lower  animals  and  the  plants  must  at  least  raise  the  question 
whether  similar  processes  do  not  occur  to  some  extent  in  higher 
forms. 

Even  in  man  and  the  other  mammals  the  different  tissues  do 
not  undergo  senescence  alike.  Certain  cells,  such  as  the  Malpighian 
layer  of  the  skin,  continue  to  divide  and  replace  the  old  dying  or 
dead  cells  of  the  epidermis,  and  remain  relatively  young  in  appear- 
ance and  behavior  throughout  the  life  and  even  after  the  death  of 
the  individual.  In  various  other  tissues  such  replacement  of  old 
differentiated,  or  dead  cells  by  younger  cells  occurs  more  or  less 
extensively  in  normal  life,  and  tissue  regeneration,  following  injury 
or  loss  of  tissue  cells,  occurs  to  a  greater  or  less  extent  in  all  tissues 
except  the  nervous  system. 

The  process  of  tissue  regeneration,  whether  in  normal  life  or  as 
a  reaction  to  injury,  undoubtedly  retards  the  aging  of  the  tissue 
or  organ  concerned  as  a  whole,  but  the  question  whether  it  involves 
an  actual  dedifferentiation  and  rejuvenescence  of  the  cells  concerned 
in  the  regeneration  must  be  briefly  considered.  Minot  ('08,  '13) 
has  attempted  to  prove  that  dedifferentiation  does  not  actuall}- 

293 


?94 


SENESCE^XE  AND  REJUVENESCENCE 


occur  in  such  cases  and  that  the  regeneration  takes  its  origin  from 
cells  or  parts  of  cells  which  have  never  undergone  differentiation, 
so  that  even  in  these  cases  development  is  progressive,  not  regres- 
sive. His  conclusions  are  based  on  the  histological  appearance, 
not  upon  the  behavior  of  the  cells.  One  of  the  cases  cited  by  him 
as  an  example  is  the  regeneration  of  striated  muscle  after  injury. 
He  points  out  that  the  only  portions  of  the  muscle  which  take  part 
in  the  regeneration  are  the  nuclei  and  the  small  accumulations  of 


Figs.  117- 122 . — Various  stages  of  regeneration  after  wounding  in  striated  muscle : 
Fig.  117,  injured  muscle  after  three  days,  showing  proliferation  of  nuclei  and  formation 
of  protoplasmic  cells;  Fig.  118,  multinucleate  masses  resulting  from  proliferation; 
Figs.  119,  120,  "muscle  buds"  at  ends  of  injured  fibers;  Fig.  121,  regenerated  fibers; 
Fig.  122,  giant  cells,  inclosing  a  piece  of  necrotic  muscle  fiber.     From  Ziegler,  '01. 


granular  undifferentiated  cytoplasm,  as  he  terms  it,  which  surround 
them.  From  these  parts  the  new  muscle  cells  arise  by  division  of 
the  nuclei  and  growth  of  the  granular  cytoplasm  (Fig.  117);  these 
cells  form  multinucleate  masses  either  along  the  course  (Fig.  118) 
or  at  the  injured  end  of  the  fibrillar  substance  (Fig.  119).  From 
the  cytoplasm  of  these  cells  new  fibrillar  substance  arises  in  con- 
tinuity with  the  old  (Figs.  120,  121).  When  these  cells  are  not  in 
contact  with  hving  muscle  substance,  as  at  b  in  Fig.  117,  they  form 


REJUVENESCENCE  AND  DEATH  295 

multinucleate  "giant  cells"  (Fig.  122),  and  these  do  not  give  rise  to 
new  fibrillar  substance,  but  usually  die  sooner  or  later.  Even  if 
Minot  is  correct  in  maintaining  that  the  fibrillar  substance  has  no 
capacity  for  regeneration,  it  is  of  interest  to  note  that  the  new 
fibrillar  substance  seems  to  arise  in  continuity  with  the  old,  while 
isolated  cells  apparently  do  not  produce  fibrillar  substance. 

The  conclusion  that  there  is  no  dcdift'erentiation  involved  in 
such  cases  is,  I  believe,  not  warranted  by  the  facts.  The  point  of 
importance  is  that  during  the  earlier  stages  of  their  developmental 
history  the  muscle  cells  produced  granular  cytoplasm  and  nuclear 
substance  and  grew  and  divided,  but  later  began  to  give  rise  to 
fibrillar  substance  and  the  proportion  of  this  substance  to  the 
nuclei  and  granular  ''undifferentiated"  cytoplasm  increased  enor- 
mously. After  injury,  however,  the  activity  of  the  muscle  cells 
changes,  and  they  produce  more  granular  cytoplasm  and  more 
nuclear  substance.  In  short,  they  have  returned  to  a  kind  of 
activity  characteristic  of  early  stages  of  embryonic  development. 
What  is  this  if  it  is  not  dediflferentiation  ?  The  fact  that  the  old 
fibrillar  substance  degenerates  instead  of  regenerating  is  quite 
irrelevant.  The  question  is  not  whether  all  parts  of  the  cells  are 
capable  of  regeneration,  but  whether  the  cells  can  again  resume  a 
kind  of  activity  characteristic  of  an  earlier  stage  of  development, 
and  the  process  of  regeneration  of  muscle  and  various  other  tissues 
in  man  and  the  higher  animals  leaves  no  doubt  that  they  possess 
this  capacity.  Even  in  the  outgrowth  of  new  nerve  fibers  from  the 
central  stump  of  a  cut  nerve  there  is  a  return  to  a  process  of  growth 
and  development  which  is  normally  characteristic  of  an  earlier 
stage  of  development.  Champy  maintains  that  dcdift'erentiation 
occurs  in  tissues  cultivated  outside  the  organism  in  nutritive 
media — the  method  often  termed  explantation — and  has  described 
at  length  the  changes  in  cultures  of  kidney  cells.'  Regression  and 
dcdift'erentiation  certainly  occur  to  a  greater  or  less  extent  in  most 
tissues  of  man  and  the  higher  animals,  but  the  apparent  inability 
of  the  cells  of  one  tissue  to  give  rise  to  other  tissues  indicates  that, 

'  See  Champy,  '13,  '14,  and  earlier  papers  which  are  included,  together  with 
manj'  other  references  bearing  upon  this  question,  in  the  bibliographic  lists  of  these 
papers. 


296  SENESCENCE  AND  REJUVENESCENCE 

at  least  under  the  usual  conditions,  regression  does  not  bring  the 
cell  back  to  a  completely  undifferentiated  stage. 

It  is  of  course  true  that  in  some  tissues,  such  as  the  skin,  the 
more  highly  differentiated  cells  show  no  capacity  for  dedifferentia- 
tion,  but  die  and  are  replaced  by  division  and  growth  of  cells  which 
remain  throughout  life  in  a  more  or  less  embryonic  condition.  In 
such  cases  there  is  no  evidence  of  regression  and  dedifferentiation, 
but  its  absence  in  the  one  tissue  does  not  justify  the  conclusion  that 
it  is  absent  in  another.  DedilTerentiation  and  regression  in  tissue 
cells  are  undoubtedly  associated  with  rejuvenescence  in  the  higher 
as  well  as  in  the  lower  organisms,  and  tissue  regeneration,  whether 
a  feature  of  normal  life  or  the  result  of  injury,  must  bring  about 
some  degree  of  rejuvenescence  in  the  parts  concerned. 

After  a  period  of  hibernation,  tissue  regeneration  is  often  very 
extensive  (Monti,  '05)  and  may  involve  tissues  which  usually  show 
but  little  regeneration.  In  such  cases  the  large  proportion  of  young 
cells  in  the  body  must  render  the  animal  as  a  whole,  though  not 
necessarily  all  parts  of  it,  appreciably  younger  than  before  hiberna- 
tion. In  fact,  the  periodic  cycle  of  activity  and  hibernation  in 
various  forms  is  in  many  respects  similar  to  an  age  cycle.  It  is 
probable  that  the  rejuvenescence  begins  during  the  hibernation 
period  when  the  animal  is  living  upon  its  own  substance,  like  the 
starving  planarian,  and  that  this  change  leads  sooner  or  later  to 
renewed  division  and  growth  of  cells.  At  the  same  time,  other 
cells  doubtless  die  and  are  later  replaced  by  the  younger  cells. 

Other  periodic  changes,  particularly  in  the  glandular  tissues, 
show  the  essential  characteristics  of  an  age  cycle.  In  the  pancreas 
cell,  for  example  (see  pp.  189-191),  the  loading  of  the  cell  is  both 
morphologically  and  physiologically  similar  to  senescence,  and  the 
discharge  to  rejuvenescence.  In  such  cases  the  changes  occur  in 
individual  cells  without  cell  reproduction. 

The  cells  of  the  nervous  system  in  man  and  many  animals  are 
believed  to  persist  throughout  life,  and  to  possess  no  appreciable 
capacity  for  regression  and  dedifferentiation  beyond  their  abihty 
to  regenerate  the  nerve  fibers  which  arise  from  them.  Doubtless 
this  belief  is  correct,  so  far  as  visible  structural  changes  or  measure- 
able  metabolic  changes  are  concerned;   but  is  there  not  reason  to 


REJUVENESCENCE  AND  DEATH  297 

believe  that  the  effect  of  a  change  in  mental  occupation  or  of  a 
vacation  after  long-continued  mental  labor  in  a  particular  field  is 
in  some  slight  degree  a  rejuvenescence  of  the  nerve  cells?  Many 
facts  indicate  that  a  reasonable  variety  in  mental  occupation  is  a 
factor  in  retarding  mental  senility.  What  we  often  call  mental 
fatigue  may  be  something  much  less  evanescent  than  fatigue  in  the 
ordinary  sense,  but  recovery  may  occur  in  time.  Verworn  ('09, 
p.  557)  has  drawn  a  distinction  between  fatigue,  resulting  from 
accumulation  of  substances  which  retard  metabolism,  and  exhaus- 
tion, resulting  from  lack  of  oxygen  or  other  substances  necessary 
for  metabolism.  Recently  Dolley  ('14)  has  maintained  that  both 
of  these  changes  may  bring  about  senility  in  the  nerve  cell.  Ex- 
haustion, I  beheve,  resembles  senility  as  death  from  asphyxiation 
resembles  death  from  old  age.  In  both  exhaustion  and  senility  the 
rate  of  oxidation  may  be  decreased,  but  the  factors  involved  and 
the  condition  of  the  organism  in  the  two  cases  are  very  different. 
Recovery  from  exhaustion  is  then  not  the  same  sort  of  change  as 
rejuvenescence  except  as  it  involves  increase  in  rate  of  oxidation. 
Fatigue  and  recovery  constitute  a  cycle  resembling  much  more 
closely  the  age  cycle.  As  I  have  pointed  out  in  chap,  viii,  it  is  im- 
possible to  draw  the  line  sharply  between  age  changes  and  various 
other  periodic  or  cyclical  changes  in  the  organism,  and,  although 
the  nervous  system  is  without  doubt  a  highly  stable  tissue,  the  ver\' 
definite  physiologically  regressive  changes  which  occur  in  recovery 
from  mental  fatigue  or  from  long-continued  mental  activity  of  a 
particular  kind  suggest  that  changes  closely  approaching  rejuvenes- 
cence occur.  Even  here  development  is  not  always  and  onh-  pro- 
gressive, as  ]Minot  and  many  others  would  have  us  believe,  but  is 
made  up  of  progressive  and  regressive  changes  with  the  balance 
greatly  in  favor  of  the  former. 

The  occurrence  of  rejuvenescence  in  connection  with  starvation 
in  planarians  raises  the  question  whether  any  changes  in  this  direc- 
tion are  associated  with  starvation  in  the  higher  animals.  The 
metabolism  of  starvation  in  man  and  the  higher  vertebrates  has 
been   extensively   studied   by   many   investigators,'   and    there   is 

'  See  the  bibliographies  in  ihe  the  article  by  Weber,  "  Cber  IIungerstolTwechsel," 
Ergcbnisse  d.  Physiol.,  I,  1902,  in  the  paper  b\'  I'embrey  and  Spriggs,  '04,  and  in  Bene- 
dict's studies  of  starvation  metabolism  in  man  (Benedict,  '07,  '15). 


298  SENESCENCE  AND  REJUVENESCENCE 

general  agreement  that  the  rate  of  metaboHsm  falls  rapidly  during 
the  early  stages  of  starvation  to  a  more  or  less  constant  level.  In 
the  later  stages  of  starvation  the  well-known  premortal  increase 
in  nitrogen  elimination  occurs,  which  most  authors  believe  to  be 
due  to  increased  breakdown  of  tissue  substance  after  the  reserves 
of  fat  have  largely  disappeared.  In  Benedict's  latest  study  of 
starvation-metabolism,  covering  a  fasting  period  of  thirty-one  days 
in  the  human  subject,  the  ox^-gen  consumption,  carbon-dioxide  pro- 
duction, and  heat  production  per  kilo  of  body-weight  show  a  slight 
increase  toward  the  end  of  the  period,  and  other  investigators  men- 
tion slight  changes  of  the  same  sort,  but  whether  these  facts  have 
any  significance  in  connection  with  rejuvenescence  is  not  yet  clear. 
While  considerable  loss  of  weight  occurs  before  death,  in  no  case 
is  there  a  degree  of  reduction  comparable  to  that  observed  in  the 
lower  invertebrates.  Apparently  the  higher  animals  are  unable 
for  some  reason  to  use  their  own  tissues  as  a  source  of  nutrition  to 
any  such  extent  as  the  lower  forms.  Probably  this  inability  is  due 
in  large  part  to  the  relatively  high  physiological  stability  of  the 
tissue  components,  but  other  factors  may  also  be  concerned. 

While  there  is  no  distinct  indication  of  any  rejuvenescence 
during  the  starvation  period,  it  has  often  been  noted  that  the  body- 
weight  after  starvation  becomes  greater  than  before.  Von  Seeland 
('87)  found  this  to  be  the  case  in  fowls  with  periodic  starvation.  The 
increase  in  weight  was  due  primarily  to  increase  in  proteids  and 
not  to  deposition  of  fat.  Noe  ('00)  obtained  similar  results  by 
periodic  starvation  of  rabbits  and  mice.  In  man  also  a  starvation 
period  is  often  followed  by  an  increase  in  vigor  and  body-weight, 
and  starvation,  properly  controlled,  is  believed  by  many  to  possess 
a  certain  therapeutic  significance. 

The  injurious  eft'ects  of  overnutrition  in  man  are  commonly 
supposed  to  be  due  in  large  measure  to  the  accumulation  of  fat  or 
to  intoxications.  The  possibility  must,  however,  be  admitted  that 
overnutrition  may  actually  increase  the  rate  of  senescence  to  some 
slight  extent  by  increasing  the  deposition  in  the  cellular  substratum, 
not  only  of  fat,  but  of  other  substances  which  aid  in  decreasing  the 
general  rate  of  metabolism.  Instances  of  longevity  in  man  on  a 
low  diet  are  not  lacking,  and  much  has  been  written  during  recent 
years  of  the  perils  of  overeating. 


REJUVENESCENCE  AND  DEATH  299 

In  certain  bacterial  diseases,  such  for  example  as  typhoid  fever, 
a  very  great  decrease  in  body-weight  may  occur,  and  it  is  often 
observed  that  the  body-weight  becomes  greater  and  the  person 
apparently  more  vigorous  after  recovery  than  })cfore  the  illness. 

These  various  facts  viewed  in  the  light  of  the  effects  of  starva- 
tion and  reduction  in  the  lower  invertebrates  indicate  that,  even  in 
man,  reduction  by  starvation  or  other  means  may  bring  about  some 
degree  of  rejuvenescence  through  the  breakdown  and  elimination 
of  constituents  of  the  cellular  substratum.  During  reduction  in 
these  cases  the  rejuvenescence  is  potential  rather  than  actual,  and 
it  becomes  apparent  only  when  recovery  occurs.  But  rejuvenes- 
cence by  reduction  is  limited  in  the  higher  animals,  for  reduction 
in  these  forms  soon  ends  in  death,  so  that  there  is  at  present  no 
immediate  prospect  of  our  being  able  to  rejuvenate  ourselves  to 
any  great  degree,  or  to  retard  senescence  or  delay  death  to  any 
great  extent  by  any  such  means.  Under  certain  conditions  long- 
continued  or  periodic  starvation  may  bring  about  an  appreciable 
rejuvenescence,  but  it  is  not  in  any  sense  a  cure-all  for  human  ills. 
There  is  not  the  slightest  doubt  that  certain  recent  books  and 
articles  on  the  therapeutic  value  of  starvation,  written  by  laymen 
who  have  experimented  on  themselves,  have  done  great  harm  to 
many  persons.  Certainly  no  one  who  desires  to  subject  himself  to 
experiment  of  this  kind  should  do  so  without  submitting  first  to  a 
thorough  medical  examination  and  to  medical  observation  and 
control  during  the  experiment.  Where  weakness  or  organic  disease 
exists,  such  experiments  may  be  only  a  means  of  aggravation  and 
so  hasten,  rather  than  delay,  death.  And  even  if  such  diseases  as 
typhoid  fever  do  in  some  cases  accomphsh  a  slight  degree  of  rejuve- 
nescence, no  one  will  be  inclined  to  regard  them  as  an  unmixed  good. 
In  too  many  cases  they  serve  only  to  develop  or  aggravate 
weaknesses  or  to  prepare  the  way  for  other  infections,  and  so  to 
shorten  life  rather  than  to  prolong  it. 

A  recent  study  of  the  susceptibility  to  the  cyanides  and  to  lack 
of  oxygen  of  fishes  during  starvation,  by  Mr.  M.  M.  Wells,"  seems 
to  indicate  that,  as  regards  the  effect  of  starvation,  the  fishes 

'  Mr.  Wells,  formerly  an  assistant  in  the  Department  of  Zoolopy  of  tlie  University 
of  Chicago,  has  not  yet  completed  his  investigations,  but  very  kindly  permits  the 
citation  of  certain  of  the  results  obtained. 


300  SENESCENCE  AND  REJUVENESCENCE 

occupy  a  position  intermediate  between  the  higher  vertebrates 
and  the  lower  invertebrates,  such  as  Planaria.  Thus  far  Mr.  Wells 
has  found  that  the  susceptibility  to  cyanide  and  lack  of  oxygen 
decreases  early  in  starvation  and  remains  more  or  less  constant 
during  the  first  month  or  six  weeks  and  then  undergoes  a  rapid 
increase  and  may  become  as  high  as  that  of  well-fed  growing  indi- 
viduals of  much  smaller  size  than  the  starved  animals  at  the  begin- 
ning of  the  experiment.  Apparently  the  rate  of  metabolism  falls 
early  in  starvation  and  remains  relatively  low  for  several  weeks  while 
decrease  in  weight  goes  on,  but  after  several  weeks  the  rate  begins  to 
rise  and  may  reach  that  of  animals  which  are  physiologically  much 
younger  than  the  starved  animals  were  at  the  beginning.  During 
the  first  part  of  the  period  the  starved  fishes  behave  as  regards  rate 
of  metabolism  like  the  warm-blooded  animals,  but  later  a  rise  in 
rate  occurs  like  that  which  the  planarians  show  from  the  beginning. 
Any  attempt  at  interpretation  of  these  results  must  at  present, 
however,  be  little  more  than  a  guess.  The  experiments  suggest 
that  after  removal  or  transformation  of  certain  constituents  of  the 
substratum  the  cells  begin  to  burn  themselves  up  at  an  increasingly 
rapid  rate  as  in  Planaria,  and  so  a  much  greater  degree  of  rejuvenes- 
cence occurs,  at  least  in  some  tissues,  than  in  the  mammals. 

It  has  long  been  known  that  frogs  and  salamanders  may  live 
for  long  periods  of  time  without  food  and  may  undergo  a  consider- 
able degree  of  reduction  during  starvation.  In  his  studies  of  the 
effects  of  starvation  on  members  of  this  group  Morgulis  ('ii,  '13) 
has  found  that  protracted  starvation  has  a  distinctly  rejuvenating 
effect.  After  starvation  the  animals  grow  more  rapidly,  use  a 
larger  percentage  of  the  nutrition  in  growth,  and  attain  larger  size 
than  those  continuously  fed.  Contrary  to  von  Seeland  (p.  298), 
Morgulis  finds  that  intermittent  starvation  has  a  stunting  effect, 
but  suggests  that  in  his  experiments  the  animals  did  not  com- 
pletely recover  between  starvation  periods. 

In  man  and  the  higher  vertebrates  and  probably  also  in  the 
higher  invertebrates,  such  as  the  insects,  individuation  and  differ- 
entiation have  progressed  so  far  that  after  the  earlier  stages  of 
development  any  considerable  degree  of  reduction  or  regression  is 
impossible  under  ordinary  conditions  without  endangering  in  one 


REJUVENESCENXE  AND  DEATH  301 

way  or  another  the  continued  existence  of  the  whole  mechanism. 
But  the  facts  indicate  that  even  in  such  organisms  some  degree  of 
regression  and  rejuvenescence  may  occur. 

LENGTH  OF  LIFE  AND  DEATH  FROM  OLD  AGE 

When  the  rate  of  metabohsm  becomes  so  low  in  consequence  of 
advancing  senescence  that  the  cell  or  organism  can  no  longer 
synthesize  its  metabolic  substratum  in  sufficient  amount  to  com- 
pensate the  losses,  atrophy  begins  and  must  sooner  or  later  end  in 
the  destruction  of  the  physiological  mechanism,  which  is  death. 

In  a  complex  organism  like  man,  different  cells  and  tissues  grow 
old  at  different  rates,  and  death  from  old  age  of  the  organism  as  a 
whole  does  not  by  any  means  imply  the  death  of  all  its  cells.  Death 
of  cells  apparently  from  old  age  occurs  from  early  stages  of  develop- 
ment throughout  the  whole  life  history,  and  we  also  know  that 
most  of  the  cells  of  the  body  do  not  die  when  death  of  the  individual 
occurs.  The  individual  dies  when  some  tissue  or  organ  which  is 
essential  for  its  continued  existence  reaches  the  point  of  death, 
and  since  the  parts  are  incapable  of  dedifferentiation  and  a  new 
individuation,  the  other  organs  or  cells  die  sooner  or  later  because 
of  lack  of  nutrition  or  oxygen,  or  because  of  the  accumulation  of 
toxic  products  of  metabolism. 

So-called  physiological  death  in  the  higher  animals  is  then  due 
to  the  breakdown  of  the  physiological  mechanism  of  the  indi- 
vidual at  some  essential  point,  and  not  to  the  simultaneous  death 
of  all  parts.  As  regards  this  fact  different  authorities  are  agreed, 
but  wide  differences  of  opinion  exist  as  regards  the  organ  or  organs 
responsible  for  breakdown  of  the  mechanism.  ]\Iuhlmann  ('00. 
'10,  '14)  and  Ribbert  ('08)  maintain  that  physiological  death  is 
essentially  a  death  of  the  brain;  Lorand  ('11),  that  the  glands  of 
internal  secretion  are  primarily  responsible;  and  Demangc  ('86) 
and  ]\letchnikoff  ('03,  '10)  regard  arteriosclerosis  as  the  most 
important  factor  in  death. 

Without  attempting  any  extended  discussion  of  these  and  other 
views,  it  may  be  pointed  out  that  the  growth  of  the  central  nervous 
system  begins  and  is  completed  earlier,  and  that  its  development  is 
apparently  more  continuously  progressive,  with  less  rejuvenescence, 


o 


02  SENESCENCE  AND  REJUVENESCENCE 


than  that  of  other  organs.  Even  in  starvation  the  nervous  system 
shows  Httle  or  no  reduction.  There  is,  therefore,  some  reason  for 
beheving  with  ^Miihhnann  and  Ribbert  that  death  from  old  age 
uncomphcated  by  disease  or  incidental  factors  is  primarily  a  death 
of  the  nervous  system,  and  both  the  histological  characteristics  of 
the  nerve  cells  and  the  physiological  condition  of  the  nervous  system 
in  cases  of  extreme  old  age  afford  support  to  this  view.  Even  in 
invertebrates  as  low  in  the  scale  as  annehds.  Harms  ('12)  has 
observed  that  the  first  structural  changes  preceding  natural  death 
occur  in  the  cephahc  portion  of  the  central  nervous  system. 

But  death  from  old  age  alone  without  any  complicating  factors 
is  undoubtedly  rare,  and  it  is  very  difficult  to  determine  in  any 
given  case  whether  complicating  factors  are  present  or  not;  con- 
sequently it  is  not  possible  to  assert  positively  that  natural  death 
is  in  all  cases  death  of  the  brain  or  nervous  system,  although  the 
evidence  points  in  that  direction. 

In  various  insects  and  in  certain  fish,  e.g.,  the  salmon,  death 
occurs  almost  at  once  after  extrusion  of  the  sexual  products.  In 
such  cases  the  factor  immediately  concerned  in  bringing  about 
death  is  probably  exhaustion  rather  than  old  age,  although  the 
organism  is  undoubtedly  in  an  advanced  stage  of  senescence  when 
sexual  maturity  is  attained.  In  certain  insects  and  some  other 
invertebrates  which  do  not  feed  in  the  adult  stage  natural  death 
is  probably  a  death  from  starvation. 

The  natural  length  of  life  of  organisms  must  depend  on  a  variety 
of  factors,  such  as  specific  constitution  of  protoplasm,  rate  of  senes- 
cence, continuity  of  progressive  development,  or  in  other  words  the 
degree  of  rejuvenescence  during  the  life  history,  functional  activity, 
perhaps  the  amount  and  in  some  forms  probably  also  the  character 
of  food.  In  general  it  represents  the  length  of  time  from  the 
beginning  of  senescence  in  the  early  stages  of  development  to  the 
stage  where  the  rate  of  metaboHsm  is  so  low  that  the  physiological 
mechanism  disintegrates.  Commonly  the  life  of  the  organism  is 
very  much  longer  than  that  of  many  of  its  constituent  cells,  but  it 
is  probable  that  the  extreme  limit  of  life  of  the  individual  is  deter- 
mined by  the  length  of  life  of  its  shortest-hved  essential  organ  or 
tissue,  and  this  must  be  the  organ  or  tissue  which  is  least  subject  to 


REJUVENESCENCE  AND  DEATH  303 

or  capable  of  regression  and  rejuvenescence  and  whose  dcveloi)- 
ment  is  consequently  most  continuously  progressive.  In  the  higher 
animals  this  organ  is  unquestionably  the  central  nervous  system. 
This  line  of  evidence,  therefore,  lends  further  support  to  the  view 
that  natural  death  is  a  death  of  the  nervous  system. 

In  the  warm-blooded  vertebrates,  where  rejuvenescence  plays 
a  minor  part  in  the  life  history,  the  length  of  life  in  a  particular 
species  is  a  more  or  less  definite  length  of  time,  because  the  rate  of 
metabolism  is  largely  independent  of  external  conditions  and  the 
rate  of  development  and  senescence  is  therefore  determined  largely 
by  internal  factors  which  are  more  or  less  constant  for  the  species. 
In  the  cold-blooded  animals,  however,  where  rate  of  metabolism  is 
dependent  on  external  temperature,  senescence  can  unquestionably 
be  retarded,  and  so  the  length  of  life  increased,  by  low  temperature. 
Moreover,  in  many  of  these  animals  long-continued  starvation 
and  extensive  reduction  may  occur  with  complete  recovery,  and 
there  is  no  doubt  that  under  such  conditions  a  greater  or  less  degree 
of  rejuvenescence  and  consequently  an  increase  in  length  of  life 
may  occur  in  some  cases.  As  regards  the  lower  invertebrates,  it 
was  shown  in  an  earlier  chapter  that  senescence  may  be  retarded 
or  inhibited  for  a  long  time  and  probably  indefinitely  by  the  simple 
means  of  underfeeding.  This  is  of  course  not  possible  in  the  higher 
animals,  for  their  most  stable  tissues  undergo  senescence  to  some 
extent  even  under  these  conditions. 

Among  the  lower  animals  and  the  plants  cell  death  occurs,  as 
in  the  higher  forms,  as  the  end  of  progressive  development,  and 
death  of  the  many-celled  individual  may  occur  if  progression  and 
senescence  are  not  balanced  by  regression  and  rejuvenescence. 
Even  in  the  unicellular  forms  reproduction  by  fission  brings  about 
some  degree  of  rejuvenescence,  and  it  is  probable  that  nuclear  and 
cell  division  in  general  accomplish  the  same  result  to  some  slight 
degree.  When  cells  lose  the  capacity  to  divide  they  differentiate, 
grow  old,  and  sooner  or  later  die.  In  short,  the  only  conclusion 
warranted  by  the  facts  is  that  death  is  everywhere  the  final  result 
of  progressive  development,  if  the  process  goes  far  enough,  but  in 
many  organisms  progressive  development  is  interrupted  by  regres- 
sive processes  connected  with  repair,  reproduction,  lack  of  food,  or 


304  SENESCENCE  AND  REJUVENESCENCE 

other  conditions,  and  the  death  point  is  never  attained  by  the  indi- 
vidual, although  even  in  such  forms  death  of  cells,  apparently  from 
old  age,  may  be  a  characteristic  feature. 

The  appearance  of  death  in  the  course  of  evolution  as  the  end 
of  the  life  history  of  the  individual  is  to  be  regarded  as  a  result  of 
the  increasing  physiological  stability  of  the  substratum  of  the 
organism  and  the  increasing  degree  of  individuation  which  the 
greater  stability  makes  possible.  These  changes  determine  a 
greater  degree  of  continuity  of  progressive  development  and  senes- 
cence and  so  less  frequent  and  less  extensive  regression,  reproduc- 
tion, and  rejuvenescence. 

As  the  evolution  of  the  individual  advances  with  its  increasing 
differentiation  and  more  intimate  correlation  of  parts,  death  as  the 
termination  of  the  individual  life  history  becomes  more  and  more 
inevitable. 

SOME  THEORIES  OF  LENGTH  OF  LIFE 

Most  authors  who  have  discussed  senescence  have  regarded 
death  as  merely  the  final  termination  of  the  processes  of  senescence, 
whatever  their  view  concerning  the  nature  of  these.  But  certain 
of  the  theories  advanced  which  concern  themselves  particularly 
with  the  problem  of  the  length  of  life  require  special  mention  here. 

Some  thirty  years  ago  Weismann  ('82,  '84)  first  stated  his  view 
that  the  cause  of  death  lies  in  the  limitation  of  capacity  for  cell 
reproduction.  In  the  unicellular  organisms,  according  to  Weis- 
mann, this  capacity  is  not  limited,  therefore  the  protozoa  do  not 
die.  In  the  multicellular  organism,  however,  only  the  germ  cells 
retain  the  capacity  for  unlimited  division;  in  the  somatic  cells  the 
number  of  possible  cell  divisions  has  been  limited  by  the  action  of 
natural  selection,  which  determines  in  general  that  life  shall  not 
continue  long  after  the  reproductive  period  is  completed.  In  later 
writings  ('92,  '04)  Weismann  has  elaborated  this  idea  further,  but 
without  essential  change.  The  theory  concerns  itself  with  the 
evolution  of  length  of  life  and  of  death  rather  than  with  the  problem 
of  the  nature  of  the  physiological  processes  involved.  Death  must 
of  course  have  occurred  before  the  length  of  life  could  be  subjected 
to  the  action  of  selection.  Weismann  maintains,  however,  that 
death  is  not  a  fundamental  characteristic  of  life,  but  an  adaptation 


REJUVENESCENCE  AND  DEATH 


j":) 


which  has  arisen  "because  unhmited  duration  of  the  life  of  the 
individual  would  be  a  senseless  luxury."  In  other  words,  death 
appeared  at  some  time  as  a  chance  variation  which  was  inherited 
and  was  of  such  value  to  the  organic  world  that  through  the  action 
of  natural  selection  it  has  become  universal  in  multicellular  organ- 
isms. Death  was  possible  in  these  forms  because  somatic  and  germ 
cells  were  separated,  while  in  the  unicellular  forms  they  are  one  and 
the  same  cell. 

The  problems  of  death  and  length  of  life  find  no  solution  in  these 
speculations.  The  occurrence  of  death  is  simply  assumed  as  the 
foundation  of  the  theory.  But  it  is  not  true  that  all  multicellular 
forms  necessarily  die.  As  I  have  endeavored  to  show,  many  forms, 
both  plants  and  animals,  may  escape  death  by  reproduction  and 
rejuvenescence  in  exactly  the  same  way  as  do  the  protozoa.  On 
the  other  hand,  there  is  every  reason  to  believe  that  if  the  protozoa 
live  long  enough  without  reproduction  they  too  die  of  old  age  and 
the  germ  cells  of  the  multicellular  forms  also  apparent!)-  undergo 
senescence  and  die  of  old  age  if  rejuvenescence  is  not  initiated  by 
fertilization  (see  pp.  403-6).  The  evidence  also  indicates  that 
death  occurs  in  general  soon  after  the  period  of  sexual  reproduction 
is  over,  not  because  of  advantage  to  the  species,  but  because  sexual 
maturity  is  a  physiological  feature  of  relatively  advanced  age.  Pro- 
gressive development,  which  ends  in  death,  except  where  interrupted 
by  regression,  is  far  advanced  when  sexual  reproduction  begins. 
And,  finally,  it  is  rather  remarkable  that  natural  selection  should 
have  succeeded  so  completely,  as  Weismann  believes  it  has,  in  elimi- 
nating the  species  in  which  death  does  not  naturally  occur. 

A  theory  of  length  of  hfe  of  a  very  different  sort,  based  pri- 
marily upon  calorimetric  investigations  on  various  domestic  mam- 
mals and  man,  has  been  advanced  by  Rubner  ('08,  '09).  From  the 
available  data  Rubner  has  calculated  the  total  energ>-  requirement 
in  calories  for  a  doubling  of  body-weight  after  birth  and  the  require- 
ment per  kilogram  of  body-weight  for  the  whole  period  of  life  after 
growth  is  completed  in  a  number  of  the  domestic  mammals  ant! 
man.  The  total  calories  required  for  the  doubling  of  weight  are 
given  in  Table  VI,  and  the  total  calories  per  kilogram  of  body- 
weight  for  the  period  after  completion  of  growth  in  Table  \I1. 


3o6  SENESCENCE  AND  REJUVENESCENCE 

The  totals  for  all  except  man  show  a  rather  close  agreement  in 
each  table,  and  while  Rubner  admits  that  the  data  on  which  these 
figures  are  based  are  not  in  all  cases  satisfactory,  he  concludes 
from  the  figures  that  the  amounts  of  energy  required,  first,  for  the 
doubling  of  weight  in  growth  and,  secondly,  for  the  maintenance  of 
each  kilogram  of  body- weight  during  adult  life,  are  the  same  in 
all  species  in  the  tables  except  man.     Man  uses  a  much  greater 

TABLE  VI 

Horse 4,512  Pig 3,754 

Cow 4,243     ■  Dog 4,304 

Sheep 3,936  Cat 4,554 

Man 28,864  Rabbit 5,066 

TABLE  VII 

Man 725,770  Dog 163,900 

Horse 163,900  Cat 223,800 

Cow 141,090  Guinea-pig. 265,500 

amount  of  energy  in  both  cases,  i.e.,  a  much  smaller  percentage  of 
the  energy  of  food  is  concerned  in  growth  and  maintenance  of  body- 
weight  in  man  than  in  the  other  mammals.  These  results  of  his  cal- 
culations lead  Rubner  to  suggest  that  the  living  substance  can 
undergo  only  a  certain  number  of  atomic  rearrangements  before 
becoming  exhausted  and  breaking  down.  According  to  this  view, 
life  is  terminated  by  the  completion  of  a  complex  chemical 
reaction. 

While  I  do  not  regard  myself  as  quahfied  to  criticize  the  methods 
of  calculation,  or  the  data  on  which  these  are  based,  though  they 
may  be  open  to  criticism  at  certain  points,  Rubner's  general  conclu- 
sion demands  consideration  on  general  biological  grounds.  Assum- 
ing the  vaHdity  of  the  data  and  methods  of  treatment,  considerable 
uniformity  in  energy  requirement  in  the  mammals  is  to  be  expected, 
for  they  are  closely  related  to  each  other,  the  rate  of  metabohsm  is 
not  widely  dift'erent  in  different  species,  and  progressive  develop- 
ment is  not  to  any  great  extent  interrupted  by  regression  and 
rejuvenescence.  The  facts  scarcely  warrant  us  in  going  beyond  the 
conclusion  that  development  is  a  similar  process  in  all  these  mam- 
malian species.     If  life  is  terminated,  not  by  the  completion  of  a 


REJUVENESCENCE  AND  DEATH  307 

complex  reaction,  as  Rubner  suggests,  but  by  changes  in  the  sub- 
stratum which  retard  metaboHsm,  the  domesticated  mammals  might 
certainly  be  expected  to  require  somewhere  near  similar  amounts 
of  energy  to  attain  the  death  point. 

Rubner  fails  entirely  to  take  into  account  the  fact  that  in  all 
the  species  under  consideration  the  length  of  life  of  different  cells 
is  very  different.  Some  die  after  a  life  which  is  short  compared 
with  the  life  of  a  whole  organism,  and  are  replaced  by  others,  so 
that  in  some  tissues  growth  and  development  continue  throughout 
the  life  of  the  animal.  Other  cells  apparently  persist  as  long  as  the 
animal  lives,  and  it  is  probably  these,  e.g.,  the  cells  of  the  nervous 
system,  which  are  primarily  responsible  for  natural  death,  as  sug- 
gested above.  Rubner's  theory  also  does  not  admit  the  possibihty 
of  rejuvenescence  except  in  connection  with  fertilization,  nor  does 
it  show  how  the  starting-point  of  the  complex  reaction  is  again 
attained  at  the  beginning  of  each  generation.  As  regards  the 
exceptional  position  of  man,  Rubner  beheves  that  the  human  living 
substance  is  different  from  that  of  other  mammals  and  requires  a 
much  larger  amount  of  energy  for  a  given  amount  of  growth. 
These  data  compare  man  with  domesticated  mammals;  if  it  were 
possible,  it  would  be  of  considerable  interest  to  determine  whether 
the  energy  requirements  are  the  same  in  wild  as  in  domesticated 
animals.  It  seems  probable  that  they  would  be  higher  in  the  wild 
forms. 

In  a  number  of  papers  Loeb  has  discussed  the  nature  of  the 
processes  which  bring  about  death  in  the  mature  egg  when  it  is  not 
fertilized  and  has  described  certain  methods  by  which  its  life  can 
be  prolonged.  In  two  papers,  however  (Loeb,  '02,  '08),  he  has 
dealt  with  the  problems  of  death  and  length  of  life  in  a  more  general 
way.  The  starfish  egg,  if  not  fertilized,  dies,  usually  within  a  few 
hours  after  maturation,  but  if  it  is  prevented  by  lack  of  o.xygen 
from  undergoing  maturation  its  life  may  be  prolonged  for  days. 
From  these  facts  Loeb  concludes  that  natural  death  in  these  cases 
is  due  to  specific  destructive  processes  which  are  set  going  by 
maturation.  These  processes  cannot  be  identical  with  the  pro- 
cesses underlying  development,  because  they  are  inhibited  or 
delayed  by  the  fertilization  of  the  egg. 


3o8  SENESCENCE  AND  REJUVENESCENCE 

In  the  second  paper  he  uses  the  temperature  coeflEicient  of  the 
length  of  hf e  of  sea-urchin  eggs  at  high  temperatures  as  a  basis  for 
his  conclusions.  To  determine  the  temperature  coefficient  of  length 
of  life  Loeb  subjects  lots  of  freshly  fertilized  eggs  of  sea-urchins  to 
different  temperatures  above  that  in  which  they  normally  develop, 
and  then,  by  removing  portions  of  each  lot  at  intervals  to  room 
temperature  and  allowing  them  to  develop,  he  finds  the  length  of 
time  at  the  high  temperature  which  is  just  necessary  to  prevent  the 
eggs  from  developing  into  normal  swimming  larvae.  The  ratio 
of  these  times  for  different  temperatures  is  the  temperature  coeffi- 
cient. These  experiments  give  a  temperature  coefficient  of  approxi- 
mately i,ooo  for  io°  C,  i.e.,  it  requires  only  about  one-thousandth 
as  long  at  30°  as  at  20°  C.  to  injure  the  eggs  so  that  they  do  not 
produce  normal  larvae.  The  temperature  coefficient  of  the  length 
of  life  of  unfertilized  eggs  Loeb  finds  to  be  about  the  same. 

The  temperature  coefficient  of  embryonic  development  in  the 
sea-urchins  is  2.86  for  10°  C,  which  means  that  a  rise  in  tempera- 
ture of  10°  increases  the  rate  of  development  2.86  times.  This 
is  about  the  usual  temperature  coefficient  of  chemical  reaction  at 
these  temperatures. 

Loeb's  argument  is  that  if  the  processes  which  determine  devel- 
opment and  those  which  determine  length  of  life  are  identical,  they 
must  have  the  same  temperature  coefficient,  and  since  they  do  not, 
he  concludes  that  they  must  be  different.  Death  is  therefore  not 
the  final  result  of  development,  but  of  specific  processes  quite  dis- 
tinct from  the  developmental  processes.  He  also  attempts  to 
account  for  the  supposed  large  numbers  of  individuals  in  the  animal 
life  of  cold  waters  on  this  basis;  at  10°,  for  example,  animals  develop 
about  one-third  as  rapidly  but  live  one  thousand  times  as  long  as  at 
20°;  therefore  the  number  of  individuals  alive  at  any  given  time 
must  be  much  greater  at  the  lower  than  at  the  higher  temperature. 

There  are  several  objections  to  this  line  of  argument.  In  the 
first  place,  the  processes  which  immediately  determine  death  may 
be  very  different  from  those  which  underlie  development,  and  still 
death  may  be  the  result  of  the  developmental  processes,  because 
these  bring  the  organism  into  a  condition  where  the  death  changes 
can  occur.     Loeb,   himself,   admits   this  when  he  says  that   the 


REJUVENESCENCE  AND  DEATH  309 

destructive  processes  which  bring  about  death  in  the  unfertilized 
egg  are  set  going  by  the  maturation  process.  Maturation  is  a 
normal  feature  of  the  hfe  history  of  the  egg,  and  to  say  that  it  leads 
to  death  is  merely  to  say  that  the  end  of  the  developmental  history 
is  death. 

As  regards  the  conclusions  drawn  from  the  temperature  coeffi- 
cient of  length  of  life,  Loeb  assumes  that  death  from  high  tempera- 
ture is  identical  with  natural  death  from  old  age,  although  there  is 
no  evidence  that  this  is  the  case.  Certainly  there  is  little  reason  for 
believing  that  the  death  of  embryos  in  early  stages  or  of  lar\^ae  is 
the  same  thing  as  the  death  from  old  age  of  full-grown  animals. 
Death  in  these  early  stages,  however  it  occurs,  is  undoubtedly  due 
to  processes  different  from  the  developmental  processes,  but  it  is  at 
the  same  time  an  indication  that  something  has  gone  wrong  and 
not  in  any  sense  a  natural  physiological  death.  To  make  an  acci- 
dental process  of  this  kind  the  basis  for  conclusions  concerning 
length  of  hfe  and  physiological  death  under  natural  conditions  is 
certainly  not  warranted  until  convincing  proof  that  the  two  are 
identical  is  presented.  Loeb  has  failed  completely  to  show  that 
the  processes  which  bring  about  death  at  high  temperature  have 
anything  to  do  with  physiological  death  in  nature  and  he  has 
presented  no  evidence  to  show  that  physiological  death  is  not  the 
result  and  final  stage  of  development. 

CONCLUSION 

As  regards  the  relation  between  senescence,  death,  and  rejuve- 
nescence, the  higher  animals  and  man  differ  from  the  lower  organisms 
in  the  limitation  of  the  capacity  for  regression  and  rejuvenescence 
under  the  usual  conditions.  Senescence  is  therefore  more  continu- 
ous than  in  the  lower  forms  and  results  in  death,  which  is  the  final 
stage  of  progressive  development.  These  characteristics  of  man 
and  the  higher  animals  are  connected  with  the  evolutionary  increase 
in  the  physiological  stabiUty  of  the  protoplasmic  substratum  and 
the  higher  degree  of  individuation  which  results  from  it.  Neverthe- 
less, some  degree  of  rejuvenescence  occurs,  even  in  man,  and  ditler- 
ent  tissues  differ  as  regards  their  capacity  for  rejuvenescence,  the 
central  nervous  system  being  apparently  least  capable  of  regressive 


3IO  SENESCENCE  AND  REJUVENESCENCE 

changes.  This  characteristic  of  the  nervous  system  suggests  the 
probabihty  that  the  natural  or  physiological  length  of  life  in  these 
forms  is  determined  primarily  by  the  length  of  hfe  of  the  nervous 
system  and  that  physiological  death  is  primarily  the  death,  as  the 
final  stage  of  senescence,  of  the  nervous  system.  This  view  is 
supported  by  various  facts  of  observation. 

Physiological  or  natural  death  is  not  something  which  has 
originated  in  the  course  of  evolution  from  the  lower  to  the  higher 
forms.  All  organisms,  from  the  lowest  to  the  highest,  from  the 
simplest  to  the  most  complex,  undoubtedly  die  of  old  age,  unless 
senescence  is  compensated  by  rejuvenescence.  In  the  lower  forms 
the  death  point  may  never  be  attained  under  the  usual  conditions 
because  the  low  stability  of  the  substratum  and  the  consequent 
low  degree  of  individuation  permit  the  frequent  occurrence  of  a  high 
degree  of  rejuvenescence.  In  the  higher  forms  death  becomes 
inevitable  and  necessary  because  the  capacity  for  rejuvenescence 
is  limited  by  the  greater  stabihty  of  the  substratum.  For  his  high 
degree  of  individuation  man  pays  the  penalty  of  individual  death, 
and  the  conditions  and  processes  in  the  human  organism  which 
lead  to  death  in  the  end  are  the  conditions  and  processes  which 
make  man  what  he  is.  The  advance  of  knowledge  and  of  experi- 
mental technique  may  make  it  possible  at  some  future  time  to 
bring  about  a  greater  degree  of  rejuvenescence  and  retardation  of 
senescence  in  man  and  the  higher  animals  than  is  now  possible,  but 
when  we  remember  that  the  present  condition  of  the  protoplasmic 
substratum  of  these  organisms  is  the  result  of  millions  of  years  of 
evolutionary  equilibration,  we  cannot  but  admit  that  this  task  may 
prove  to  be  one  of  considerable  difficulty. 

REFERENCES 
Benedict,  F.  G. 

1907.     "The  Influence  of  Inanition  on  Metabolism,"  Carnegie  Inst.  Pub!., 

No.  77. 
191 5.     "A  Study  of  Prolonged  Fasting,"  Carnegie  Inst.  PubL,  No.  203. 
Champy,  C. 

1913.  "La  differenciation  des  tissus  cultives  en  dehors  de  Forganisme," 
Bibliogr.  Anal.,  XXIIl. 

1914.  "Notes  de  biologie  cytologique.     Quelques  resultats  de  la  methode 
de  culture  de  tissus:  III,  Le  rein,"  Arch,  de  zool.  exp.,  LIV. 


REJUVENESCENCE  AND  DEATH  311 

Demange. 

1886.    Elude  clinique  et  anatomo-pathologique  de  la  vieiltesse. 

DOLLEY,  D.  H. 

1914.  "On  a  Law  of  Species  Identity  of  the  Nucleus-Plasma  Norm  for 
Nerve  Cell  Bodies  of  Corresponding  Type,"  Journal  of  Comp. 
Neurol.,  XXIV. 

Harms,  W. 

191 2.  "Beobachtungen  iiber  den  natiirlichen  Tod  der  Tiere.  I.  Mitt. 
Der  Tod  bei  Hydroides  pectinata  Phil.,  nebst  Bemerkungen  iiber 
die  Biologic  dieses  Wurmes,"  Zool.  Anzeiger,  Bd.  XL. 

LOEB,  J, 

1902.  "tJber  Eireifung,  natiirlichen  Tod  und  Verlangerung  des  Lebens 
beim  Seesternei,"  Arch.  f.  d.  ges.  Physiol.,  XCIII. 

1 90S.  "tJber  den  Temperaturkoeffizienten  fiir  die  Lebensdauer  kalt- 
blutiger  Tiere  und  iiber  die  Ursache  des  natiirlichen  Todes," 
Arch.f.  d.  ges.  Physiol.,  CXXIV. 

LORAND,  A. 

191 1.    Das  Altern,  seine  Ursachen  und  seine  Behandlung.    Leipzig. 
Metchnikoff,  E. 

1903.  The  Nature  of  Man.     English  translation:  New  York  and  London. 

19 10.  The  Prolongation  of  Life.  English  translation:  New  York  and 
London. 

MiNOT,     C.  S. 

1908.     The  Problem  of  Age,  Growth  and  Death.     New  York. 

1913.  Moderne  Probleme  der  Biologie.    Jena. 

Monti,  R. 

1905.  "II  rinnovamento  dell'  organismo  dopo  il  letargo."  Monitore  Zool. 
Ital.,  XVI. 

MORGULIS,  S. 

1911.  "Studies  of  Inanition  in  Its  Bearing  upon  the  Problem  of  Growth," 
Arch.  f.  Entwickelungsmech.,  XXXII. 

1913.  "The  Influence  of  Protracted  and  Intermittent  Fasting  upon 
Growth,"  Am.  Nat.,  XLVIL 

^MtJHLMANN,  M. 

1900.     Uber  die  Ursache  des  Alters.     Wiesbaden. 

1910.  "Das  Altern  und  der  physiologische  Tod,"  Sammlung  anat.  u. 
physiol.  Vortr.,  XI. 

1914.  "Beitrage  zur  Frage  nach  der  Ursache  des  Todes,"  Arch.  f.  Pathol. 
(Virchow),  CCXV. 

NOE,  J. 

1900.  "La  reparation  compensatrice  apres  la  jcune,"  Compt.  rend,  de  la 
Soc.  biol.,  LII. 


312  SENESCENCE  AND  REJUVENESCENCE 

Pembrey,  M.  S.,  and  Spriggs,  E.  I. 

1904.     "The  Influence  of  Fasting  and  Feeding  upon  the  Respiratory  and 
Nitrogenous  Exchange,"  Jour,  of  Physiol.,  XXXI. 

RiBBERT,  H. 

1908.     Dcr  Tod  aus  Alter sschwdche.     Bonn. 

RUBNER,  M. 

1908.  Das  Problem  der  Lebensdauer  und  seine  Bezichungen  zu  Wachstum 
mid  Erndhning.     Miinchen. 

1909.  Kraft  und  Stojf  im  Haushalte  der  Natur.     Leipzig. 

Seeland,  von. 

1887.     "tJber  die  Nachwirkung  der  Nahrungsentziehung  auf  die  Ernah- 
rung,"   Biol.  Centralbl.,  VII. 

Verworn,  M. 

1909.     Allgemeine  Physiologie.     V.  Auflage.     Jena. 

Weismann,  a. 

1882.     Uber  die  Dauer  des  Lebens.     Jena. 

1884.     Uber  Leben  und  Tod.     Jena. 

1892.     Das  Keimplasma.     Jena. 

1904.     Vortrdge  uber  Descendenztheorie.    II.  Auflage.    Jena. 

ZlEGLER,  E. 

1901.  Allgemeine  Pathologie.   X.  Auflage.    Jena. 


PART  IV 

GAMETIC  REPRODUCTION  IN  RELATION  TO  THE  AGE  CYCLE 


CHAPTER  XIII 

ORIGIN  AND  I^IORPHOLOGICAL  AND  PHYSIOLOGICAL  CONDITION 
OF  THE  GAMETES  IN  PLANTS  AND  ANIMALS 

THE  THEORETICAL  SIGNIFICANCE  OF  GAMETIC  ORIGIN 

The  question  of  the  origin  of  the  gametes  or  sex  cells  derives  its 
chief  importance  from  the  germ-plasm  theory,  first  advanced  by 
Galton  ('72)  and  Jager  ('77)  and  later  developed  by  Weismann 
('85,  '92) ,  which  postulates  the  continuous  existence  of  a  germ  plasm 
independent  of  the  soma— that  is,  of  other  parts  of  the  organism— 
except  for  nutrition,  and  giving  rise  to  the  gametes.  If  such  a 
germ  plasm  exists  and  is  continuous  from  generation  to  generation 
we  should  expect  to  find  in  at  least  some  organisms  indications  of 
the  separate  existence  of  germ  plasm  and  soma,  even  in  early  stages 
of  development.  An  early  segregation  of  the  germ  plasm  from  the 
somatic  cells  has  been  recorded  for  various  animals  and  these  facts 
have  commonly  been  regarded  as  affording  support  to  the  germ- 
plasm  hypothesis.  Other  facts,  such  as  the  formation  of  gametes 
and  the  occurrence  of  regeneration  from  apparently  differentiated 
cells  in  some  animals  and  in  plants,  forced  Weismann  to  assume  the 
existence  of  a  "  supplementary  germ  plasm ''  which  was  supposed  to 
exist  in  the  nuclei  of  many  differentiated  cells  and  which  might  be 
"activated"  under  the  proper  conditions  and  give  rise  to  new 
embryonic  cells,  or  even  to  gametes.  The  existence  of  this  supple- 
mentary germ  plasm  may  be  assumed  wherever  it  is  necessary  for 
the  theory,  so  that  a  vicious  circle  is  established. 

But  when  we  consider  the  facts  apart  from  theoretical  considera- 
tions, we  find  that  the  gametes  appear  to  be  integral  parts  of  the 
organism  when  they  arise,  that  they  become  highly  specialized  and 
differentiated  cells,  and  that  fertihzation,  whatever  the  nature  of 
its  mechanism,  initiates  a  process  of  dedifferentiation  and  rejuve- 
nescence which  is  followed  by  another  period  of  differentiation  and 
senescence.  This  and  the  two  following  chapters  are  concerned 
with  the  development  of  this  point  of  view. 

315 


3i6  SENESCENCE  AND  REJUVENESCENCE 

THE  ORIGIN  OF  THE  GAMETES  IN  PLANTS 

Thus  far  no  evidence  has  been  discovered  among  the  plants  of  an 
early  separation  of  the  primitive  germ  cells  from  other  so-called 
somatic  portions  of  the  organism,  such  as  has  been  described  for 
various  animals  (see  pp.  323-33).  No  Keimhahn  or  germ  path 
exists  in  the  plants,  that  is,  the  germ  cells  cannot  be  followed  through 
the  developmental  history  as  cells  or  protoplasmic  regions  distinct 
from  other  parts  of  the  body. 

In  that  group  of  the  green  algae  known  as  the  Conjugales, 
which  includes  Spirogyra  and  the  desmids,  in  the  diatoms,  and 
in  most  of  the  ciliate  infusoria  among  the  animals,  the  cell  which 
constitutes  the  body  of  the  organism  becomes  the  gamete  without 
any  or  with  comparatively  little  visible  structural  change;  two 
such  cells  conjugate,  and  their  contents  fuse  to  form  the 
zygospore. 

In  other  algae  and  in  those  fungi  in  which  gametic  reproduction 
is  known  to  occur,  the  gametes  are  always  more  or  less  different 
both  in  morphological  structure  and  behavior  from  other  parts  of 
the  organism,  but  they  originate  from  the  plant  body  and  to  all 
appearances  are  the  most  highly  specialized  parts  of  the  species, 
and,  finally,  in  most  cases,  show  a  high  degree  of  sexual  differentia- 
tion, as  the  following  figures  show.  Fig.  123  shows  the  young  egg 
cell  of  Volvox,  Fig.  124  a  Volvox  spermatozoid.  Fig.  125  the  oogonium 
and  antheridium  of  the  alga  Oedogoniimi  with  female  and  male 
gametes,  Fig.  126  the  sex  organs  of  Chara  with  the  single  egg  in  the 
oogonium,  and  Fig.  127  a  spermatozoid  of  Chara.  In  Fig.  128 
the  sex  organs  of  the  fungus  Saprolegnia  and  their  relation  to  the 
vegetative  part  of  the  plant  are  shown.  In  all  these  cases 
the  gametes  show  the  same  sort  of  sexual  differentiation  as  in  the 
multicellular  animals.  In  the  mold  Mucor,  however,  the  ends  of 
two  hyphae  enlarge  and  come  together,  and  a  gametic  cell  is  sepa- 
rated from  each  (Fig.  129),  but  the  two  cells  are  not,  so  far  as 
known,  sexually  differentiated.  These  two  cells  increase  in  size 
(Fig.  130)  and  unite  to  form  the  zygospore  (Fig.  131).  In  none 
of  these  cases  is  there  any  trace  of  an  early  segregation  of  the  germ 
cells  from  the  rest  of  the  plant.  The  sex  organs  and  germ  cells 
appear  only  when  the  plant  attains  a  certain  physiological  condition. 


THE  GAMETES  IN  PLANTS  AXD  AMAIALS  317 


Figs.  123-127.— Gametes  of  various  algae:  Fig.  123,  young  egg  cell  of  Volvox 
aureus,  connected  with  surrounding  vegetative  cells  by  numerous  plasmatic  strands 
(from  Klein,  '89) ;  Fig.  1 24,  spermatozoid  of  Volvox  aureus  (from  Klein.  'Sq) ;  Fig.  1 25. 
part  of  iilament  of  Ocdogouium,  showing  oiigonium  with  large  egg  and  below  three 
antheridia,  from  two  of  which  spermatozoids  have  escaped  (from  Coulter,  etc.,  '10); 
Fig.  126,  branch  of  Chara,  bearing  oogonium,  og,  containing  a  single  egg  and  anlhcrid- 
ium,  an  (after  Sachs,  from  Coulter,  etc.,  '10);  Fig.  127,  spermatozoid  of  Chara  (from 
Belajefr,  '94). 


,i8 


SENESCENCE  AND  REJUVENESCENCE 


In  the  mosses  and  ferns  the  separate  history  of  the  germ  cells 
may  in  the  male  extend  back  to  an  early  stage  in  the  development 
of  the  male  sexual  organ,  the  antheridium,  where  the  sperma- 
togenous  cell  or  cells  become  separated  from  the  cells  of  the 
antheridial  wall.  Fig.  132  shows  the  stage  of  development  of  the 
antheridium  in  which  the  spermatogenous  cells  first  become  segre- 
gated in  Riccia,  one  of  the  liverworts.     After   their   segregation 


Figs,  i 28-131. — Gametes  of  fungi:  Fig.  128,  oogonium  of  Saprolegnia,  contain- 
ing several  eggs  and  antheridial  tube  piercing  its  wall  in  fertilization  (from  Coulter, 
etc.,  '10);  Figs.  1 29-131,  three  stages  in  formation  and  union  of  gametes  in  Mncor 
(from  Brefeld,  '72). 


the  spermatogenous  cells  undergo  numerous  divisions  and  finally 
give  rise  to  spermatozoids. 

The  female  gamete,  on  the  other  hand,  is  not  separated  from 
other  non-gametic  cells  until  the  last  division  preceding  fertilization. 
Figs.  133-39  show  the  development  of  the  archegonium  of  Riccia. 
The  divisions  of  the  central  cell  in  Fig.  135  produce  the  four  neck 
canal  cells  and  the  ventral  cell  (Fig.  137).  Fig.  138  shows  the 
division  of  the  ventral  cell  which  gives  rise  to  the  ventral  canal 


THE  GAMETES  IN  PLANTS  AND  ANIMALS 


319 


cell  and  the  egg.  The  fully  developed  archegonium,  containing 
the  egg  0,  is  shown  in  Fig.  139.  The  canal  cells  take  no  part  in 
reproduction,  but  degenerate  before  fertilization. 


132      © 


138  © 


133  © 


135 


134  © 


136© 


137     © 


139  © 


Figs.  132-139. — Stages  of  gamete  formation  in  the  liverwort  Rice  id :  lii;.  13.', 
antheridium  in  stage  at  which  spermatogenous  cells  become  segregated  from  cells 
of  wall;  Figs.  133-139,  formation  of  archegonium  and  egg,  0,  in  Riccia.  From  Coulter, 
etc.,  '10. 


320 


SENESCENCE  AND  REJUVENESCENCE 


In  the  seed  plants  the  whole  gametophyte  generation  is  greatly 
reduced  and  represents  scarcely  more  than  specialized  male  and 
female  organs  of  the  plant.  In  the  lower  seed  plants,  the  gymno- 
sperms,  a  considerable  number  of  nuclear  divisions  may  occur  in 
the  development  of  the  gametophyte,  and  the  female  gamete  is 
separated  from  other  cells  at  some  stage  of  this  development. 
In  the  male  gametophyte  of  the  gymnosperms  the  number  of 
divisions  varies,  but  is  always  small,  and  in  the  course  of  these 
divisions  the  male  gamete  is  separated  from  non-reproductive 
cells. 

And  finally  in  the  angiosperms,  which  represent  the  final  stage 
in  reduction  of  the  gametophyte,  the  development  of  the  male 

gametophyte — the  mature  pollen 
grain — from  the  microspore  con- 
sists, with  one  exception,  of  only 
two  nuclear  divisions,  of  which  the 
first  separates  the  primary  sper- 
matogenous  cell  from  the  tube 
nucleus  and  the  second  divides 
the  spermatogenous  nucleus  into 
two  male  gametes,  so  that  the 
male  gametophyte  contains  only 
three  nuclei  (Fig.  140). 

The  course  of  development  of 
the  female  gametophyte,  which  is 
the  embryo  sac  within  the  ovule, 
is  indicated  in  Fig.  141.  The 
nucleus  of  the  megaspore  {A)  divides  and  the  two  daughter  nuclei 
pass  to  opposite  poles  (B);  a  second  di\ision  occurs  in  each  (C), 
and  a  third  follows  (D),  so  that  eight  nuclei  are  present,  four  at  each 
pole,  but  without  cell  boundaries.  Two  nuclei,  one  from  each  group 
of  four,  move  toward  the  middle  of  the  embryo  sac  and  fuse  to  form 
the  primary  endosperm  nucleus.  About  the  three  nuclei  at  the 
micropylar  end  (the  upper  end  in  the  figures)  three  naked  cell  bodies 
arise,  and  these  three  cells  are  the  egg  and  the  two  synergids  (£). 
The  three  nuclei  at  the  opposite  pole  form  the  three  antipodal  cells 
which  are  usually  ephemeral  but  may  persist.     Thus  the  germ 


Fig.  140. — Pollen  grain  ol  Silphium 
terebinthinaceum,  showing  rounded 
vegetative  nucleus  and  the  two  elon- 
gated male  nuclei.    From  Merrell,  '00. 


THE  GAMETES  IN  PLANTS  AND  ANIMALS 


321 


plasm  is  segregated  only  at  the  last  division  preceding  ihc  rin;d 


differentiation  of  the  ess: 


Fig.  141. — Development  of  female  gametophyte  and  formation  of  egg  in  the 
higher  seed  plants:  ^,  megaspore  in  the  ovule;  B,  first  division;  C,  second  division; 
D,  third  division;  E,  mature  gametophyte:  0,  egg;  5,  syncrgids;  <j,  ;uilip»Kiais;  /, 
primary  endosperm  nucleus.     After  Coulter,  etc.,  '10. 


322  SENESCENCE  AND  REJUVENESCENCE 

The  whole  process  of  development  of  the  gametes  in  the  plants 
bears  all  the  marks  of  a  highly  specialized  process,  far  removed  from 
anything  which  occurs  in  unspecialized  embryonic  cells,  and  no- 
where do  we  find  a  separation  of  the  gametic  from  the  somatic 
material  before  the  later  or  final  stages  of  the  developmental 
process. 

The  occurrence  among  mosses,  ferns,  and  seed  plants  of  what  is 
known  as  apogamy,  i.e.,  the  formation  of  a  sporophyte  without 
fertilization  from  a  vegetative  cell  of  the  gametophyte  instead  of 
from  the  egg,^  is  of  interest  in  this  connection.  In  apogamous 
ferns  the  embryo  apparently  may  rise  from  any  vegetative  cell  of 
the  prothallium,  which  is  the  gametophyte,  and  in  seed  plants  it 
may  arise  either  from  the  synergids  or  the  antipodals  of  the  embryo 
sac,  or  from  both.  In  some  cases  also  among  angiosperms  sporo- 
phytes  may  arise  from  cells  of  the  nucellus  or  of  the  integument 
adjacent  to  the  embryo  sac.  These  cells  are  not  even  parts  of  the 
gametophyte,  but  belong  to  the  sporophyte  generation,  yet  in  the 
region  of  the  embryo  sac  they  may  produce  embryos  and  sporo- 
phytes  as  does  the  egg.  In  such  cases  the  gametophyte  generation 
is  omitted  from  the  life  history. 

All  of  these  cases  of  non-sexual  development  from  vegetative  or 
"somatic"  cells  of  the  sporophyte — the  generation  which  usually 
develops  from  the  fertilized  egg — indicate  that  the  capacities  of  the 
egg  are  not  fundamentally  different  from  those  of  other  cells  of  the 
gametophyte  and  of  some  cells  of  the  sporophyte.  It  is  of  course 
easy  to  assume  with  the  Weismannians  that,  in  spite  of  their 
visible  differentiations,  all  such  cells  contain  an  undifferentiated 
germ  plasm,  but,  so  far  as  scientific  analysis  is  concerned,  this 
assumption  is  equivalent  to  begging  the  whole  question.  A  simpler 
view  and  one  much  more  nearly  in  accord  with  the  facts  of  observa- 
tion and  experiment  is  that  which  is  held  by  most  botanists,  viz., 
that  many,  or  in  some  plants  all,  specialized  or  differentiated  cells 
may  under  proper  conditions  lose  their  specialization  and  become 
embryonic  and  so  give  rise  to  new  individuals.^ 

'  See  Winkler,  '08,  for  a  general  survey  and  bibliography  of  the  subject. 
^  In  the  usual  course  of  development  all  the  cells  of  the  gametophyte  have  the 
reduced  or  haploid  number  of  chromosomes  like  the  animal  egg  after  maturation, 


THE  GAMETES  IN  PLANTS  AND  ANIMALS  323 

It  was  shown  in  an  earlier  chapter  (pp.  245-47)  that  dcdiffcr- 
entiation  undoubtedly  occurs  very  commonly  in  plants,  especially 
in  connection  with  adventitious  and  experimental  reproduction. 
The  new  plants  thus  formed  from  cells  previously  differentiated  as 
parts  of  other  plants  possess  the  capacity  to  form  gametes.  In 
other  words,  gametes  may  very  often  arise  from  cells  which  form 
differentiated  parts  of  the  plant  body,  and  there  is  no  evidence  of 
the  continuous  existence  of  any  germ  plasm  in  the  theoretical  sense 
in  such  cells. 

To  sum  up,  we  find  in  the  plants  no  indication  of  continued  or 
early  segregation  of  germ  plasm  from  somatic  plasm.  In  most 
cases  the  gametes  are  not  separated  from  somatic  cells  until  the  final 
stages  of  their  developmental  history,  and  on  the  other  hand 
differentiated  cells,  in  many  cases  every  cell  of  the  plant,  may 
undergo  dedifferentiation  and  redifferentiation  into  new  indi- 
viduals capable  of  producing  gametes.  Either  all  the  cells  of  the 
plant  contain  germ  plasm  or  there  is  no  continuity  of  germ  plasm 
in  the  plant.  The  facts  point  to  the  second  of  these  alternatives. 
The  gametes  arise  in  the  course  of  development  like  other  specialized 
parts,  and  like  these  also  possess  a  definite  history  of  differentiation. 

THE  ORIGIN  OF  THE  GAMETES  IN  ANIMALS 

In  many  of  the  unicellular  animals,  as  in  the  unicellular  plants, 
the  cell  which  constitutes  the  organism  becomes  the  gamete.  In 
others  the  gametes  are  different  in  form  from  the  vegetative  stages, 

the  process  of  reduction  occurring  in  the  formation  of  the  spores  which  give  rise  to  the 
gametophyte.  But  in  various  mosses  and  ferns  apospory  may  occur,  i.e.,  the  gameto- 
phyte  may  arise  from  other  cells  of  the  sporophyte  without  the  occurrence  of  chromo- 
some reduction,  in  which  case  the  cells  of  the  gametophyte,  including  the  egg,  possess 
the  full  or  diploid  number  of  chromosomes.  Where  the  gametophyte  jiossesscs  the 
haploid  number  of  chromosomes,  apogamy  gives  rise  to  a  sporophyte  with  the  haploid 
number,  half  the  number  characteristic  of  sporophytes,  but  when  the  gameto- 
phyte cells  are  diploid,  the  sporophyte  which  arises  apogamously  or  parthenogeni- 
cally  possesses  the  full  number.  Various  other  combinations  of  apospory,  apogamy, 
parthenogenesis,  and  fertilization  have  been  recorded.  In  certain  mosses,  for  example, 
the  aposporous  formation  of  diploid  gametes,  followed  by  fertilization  and  the  develop- 
ment of  a  tetraploid  sporophyte,  has  been  observed  (Marchal,  '07,  '00,  '11,  '12).  The 
number  of  chromosomes  is  evidentlj'  not  connected  in  any  essential  way  either  with 
the  differentiation  of  sporophyte  and  gametophyte  or  with  the  formation  of  the 
gametes,  since  any  of  these  stages  may  possess  either  the  diploid  or  haploid  number. 


324  SENESCENCE  AND  REJUVENESCENCE 

and  sometimes  spermatozoa  and  eggs  approaching  in  morphological 
differentiation  those  of  the  multicellular  forms  appear.  In  the 
multicellular  animals  the  process  of  gamete  formation  differs  in 
certain  respects  from  that  in  the  plant.  There  is  in  the  animal  no 
developmental  history  with  cell  division,  growth,  and  differentiation 
between  maturation  and  fertilization,  corresponding  to  the  gameto- 
phyte  generation  in  plants.  The  gametic  cells  are' segregated  from 
other  cells  long  before  the  maturation  divisions  occur.  Since  the 
germ-plasm  theory  has  found  its  adherents  chiefly  among  zoologists, 
it  is  natural  that  the  attention  of  zoological  investigators  should 
have  been  attracted  to  the  question  of  the  early  segregation  of  the 
germ  cells  from  the  somatic  cells.  If  the  germ  plasm  is  really  a 
distinct  and  separate  entity  independent  of  the  soma  and  is  con- 
tinuous from  one  generation  to  another,  we  should  expect  the  germ 
cells  to  be  segregated  from  the  somatic  cells  at  the  beginning  of 
embryonic  development.  Thus  far,  however,  no  case  has  been 
discovered  in  which  such  a  segregation  occurs,  although  in  various 
animal  groups  a  more  or  less  complete  segregation  apparently  does 
occur  at  an  early  stage  of  development.  In  other  groups,  among 
the  animals,  no  indication  of  such  segregation  has  ever  been  ob- 
served, although  theoretical  considerations  have  led  many  zoolo- 
gists to  beheve  that  even  in  such  cases  a  segregation  occurs,  but 
without  visible  differences  between  germ  cells  and  other  cells. 

To  discuss  this  subject  at  length  is  beyond  the  present  purpose, 
but  some  of  the  more  important  cases  of  early  segregation  must  be 
briefly  considered.'  Perhaps  the  most  striking  case  of  early  segre- 
gation of  germ  cells  is  that  in  the  parasitic  worm  Ascaris  megalo- 
cephala,  first  described  by  Boveri  and  later  confirmed  by  other 
investigators,  but  recently  denied  by  Zacharias.^  As  every  zoolo- 
gist knows,  the  process  of  segregation  of  the  germ  cells  in  this 
species  begins  at  the  first  cleavage  of  the  egg  and  is  accompanied 
by  the  peculiar  process  of  "diminution"  of  the  chromatin  in  the 
somatic  cells.     Diminution,  which  occurs  first  in  one  cell  of  the 

'  For  general  surveys  of  the  subject  with  bibliographies  see  Korscheldt  and 
Heider, '02,  pp.  368-77;  Waldeyer,  '06;  Felix  and  Buhler,  '06;  Hacker,  '12a, '126; 
Hegner,  '14c. 

=  Boveri,  '87,  '99,  '04;   zur  Strassen,  '96;   Zacharias,  '13;   Zoja,  '96. 


THE  GAIMETES  IN  PLANTS  AND  ANIMALS  325 

two-cell  stage,  consists  in  the  separation  of  the  large  club-shaped 
ends  of  the  chromosomes,  their  exclusion  from  the  nucleus  of  the 
following  resting  stage,  and  their  gradual  disappearance  in  the 
cytoplasm.  At  the  same  time  the  remaining  portions  of  each 
chromosome  break  up  into  a  number  of  smaller  chromosomes  and 
in  following  divisions  of  this  cell  similar  small  chromosomes  appear, 
and  the  nuclei  of  the  resting  stages  are  relatively  small  and  poor 
in  chromatin.  In  the  other  cell,  however,  diminution  does  not 
occur,  the  chromosomes  retain  their  original  form  and  large  size, 
and  the  resting  nucleus  is  large  and  rich  in  chromatin.  In  the 
second  cleavage  this  cell  gives  rise  to  one  cell  which  undergoes 
diminution  and  one  which  dees  not,  and  in  the  third  and  fourth 
cleavages  also  one  cell  remains  with  chromatin  undiminished.  In 
the  fifth  cleavage  the  undiminished  cell  divides  into  two  equal  cells, 
and  these  are,  according  to  Boveri  and  others,  the  primitive  germ 
cells.  Here  then  we  can  trace  the  line  of  descent  of  the  germ  cells, 
the  germ  path  {Keimhahn),  from  the  first  cleavage.  The  germ 
path  and  the  fates  of  the  various  cells  which  undergo  diminution 
are  indicated  in  Fig.  142. 

The  process  of  early  segregation  of  germ  cells  in  Ascarls  has  been 
very  generally  regarded  as  constituting  almost  a  demonstration 
of  the  continuity  and  independence  of  the  germ  plasm,  but  as  a 
matter  of  fact  it  is  far  from  being  anything  of  the  kind.  In  the 
first  place,  while  it  seems  fairly  certain  that  the  reproductive  organs 
of  Ascaris  do  arise  from  the  undiminished  cell  line  of  descent,  it  is 
not  known  whether  these  cells  give  rise  merely  to  the  germ  cells  or 
to  the  walls  of  the  reproductive  organs  as  well.  In  the  latter  case 
the  germ  path  of  early  cleavage  has  not  resulted  in  the  segregation 
of  germ  plasm  from  the  soma,  but  merely  in  the  segregation  of 
different  organs,  for  the  walls  of  the  reproductive  organs  are  not 
germ  plasm. 

Moreover,  the  whole  process  is  very  different  from  what  we 
should  expect  in  a  segregation  of  germ  plasm  from  the  soma.  If 
the  germ  plasm  is  a  distinct  entity,  why  should  it  not  become 
segregated  in  the  first  division  instead  of  in  the  fourth  ?  The  first 
four  cleavages  are  really  segregations  into  different  cells,  not  simply 
of  germ  plasm,  but  of  various  parts  of  the  body,  as  Fig.  14-^  shows. 


326 


SENESCENCE  AND  REJUVENESCENCE 


The  diminished  cell  S,  of  the  two-cell  stage  produces  a  definite  part 
of  the  ectoderm,  and  the  cells  S„  S^,  and  S^  of  following  generations 
each  have  a  definite  fate.  In  other  words,  various  portions  of  the 
soma  or  body  are  segregated  before  the  so-called  germ  plasm. 


Entoderm  II 

and 
Mesoderm  III 


Entoderm 


Mesoderm  I 

and 
Stomodeum 


Primitive  germ  cells 


Mesoderm  II 


Fig.  142. — Diagram  of  the  cell  lineage  in  the  early  cleavage  of  Ascaris  mcgalo- 
cephala:  the  black  circles  represent  cells  before  chromatin  diminution  and  the  primitive 
germ  cells  which  do  not  undergo  diminution;  the  unshaded  circles  with  four  black  dots 
about  them  represent  the  cells  which  undergo  diminution,  and  the  unshaded  circles 
alone,  the  cells  after  diminution.  The  further  history  of  the  various  groups  of  cells 
is  indicated  by  the  words,  "ectoderm,"  etc.     After  Boveri,  '10. 

The  undiminished  cells  show  in  all  cases  a  slower  rate  of  division 
than  those  in  which  diminution  has  occurred,  and  there  is  no  evi- 
dence to  show  that  the  differences  in  the  behavior  of  the  chromatin 
are  anything  more  than  visible  indications  or  expressions  of  differ- 
ences in  rate  of  metaboHc  activity.  It  is  quite  possible  that  the 
undiminished  cells  become  germ  cells  because  they  have  a  low 


THE  GAMETES  IN  PLANTS  AND  ANIMALS 


327 


rate  of  metabolism  and  are  not  involved  in  the  early  differentiations, 
but  differentiate  later. 

A  recent  study  of  modified  cleavage  made  by  Boveri  ('10)  on 
polyspermic  and  centrifuged  eggs  of  Ascaris  has  proved  beyond  a 
doubt  that  the  occurrence  or  non-occurrence  of  chromatin  diminu- 
tion in  a  nucleus  depends,  not  upon  its  qualitative  constitution, 
but  upon  its  cytoplasmic  environment.  If  this  is  true,  persistence 
of  the  undiminished  condition  is  not  a  segregation  of  preformed 
germ  plasm,  but  a  nuclear  reaction  to  cytoplasmic  conditions.  The 
"germ  path"  is  a  feature  of  the  cytoplasm,  not  of  the  nucleus,  and 
the  cytoplasm  is  not,  properly  speaking,  a  part  of  the  germ  plasm 
at  all,  but  represents  the  soma  of  the  cell.     Which  nuclei  shall 


143 


Figs.  143,  144.— First  and  second  division  in  egg  of  Cyclops,  showing  at  one  pole 
of  spindle  the  granules  which  mark,  the  germ  path.     From  Amma,  '11. 

become  the  nuclei  of  germ  cells  is  determined,  not  primarily  by 
the  nuclei  themselves,  but  by  the  soma  of  the  cell;  the  germ  plasm 
is  not  then  an  independent  entity,  but  is  determined  by  correlative 
factors,  like  any  other  part  of  the  organism,  except  the  apical  or 
head  region. 

Hacker  ('97,  '02)  has  described  a  germ  path  for  Cyclops  and  other 
copepod  Crustacea,  and  his  observations  have  been  confirmed  by 
Amma  ('11).  The  germ  path  in  this  case  is  characterized  by  cer- 
tain granules  which  appear  at  one  pole  of  the  first  cleavage  spiniUe 
(Fig.  143),  pass  into  one  of  the  two  daughter  cells,  and  later  aggre- 
gate into  larger  masses  and  disappear.  At  the  second  division 
(Fig.  144)  and  also  at  the  third  and  fourth  divisions  similar  granules 


328  SENESCENCE  AND  REJUVENESCENCE 

appear  at  one  pole  of  the  spindle  of  the  cell  to  which  the  granules 
passed  in  the  preceding  division,  and  in  each  case  pass  into  one  of 
the  two  daughter  cells,  which  continues  the  germ  path.  But  in 
the  cell  of  the  fifth  generation  the  granules  appear  all  around  the 
mitotic  figure  and  pass  into  both  daughter  cells,  which  are  according 
to  Hacker  the  primitive  germ  cells.  Here  the  germ  path  is  charac- 
terized, not  by  peculiar  nuclear  features,  but  by  cytoplasmic  differ- 
entiations which  are  products  of  metaboHsm:  the  germ  cells  are 
evidently  an  integral  physiological  part  of  the  organism.  Some- 
what similar  germ  paths  have  been  described  for  various  other 
Crustacea. 

The  early  segregation  of  the  primitive  germ  cells  in  Sagitta  has 
been  noted  by  several  authors,  and  Buchner  ('lo)  has  recently 
discovered  the  beginning  of  the  germ  path  in  the  granules  resulting 
from  the  degeneration  of  a  nutritive  cell  taken  up  by  the  egg  in 
the  ovary,  again  a  cytoplasmic  not  a  nuclear  basis  of  segregation, 
although  the  granules  in  this  case  may  be  of  nuclear  origin.  In  a 
discussion  of  other  cases  Buchner  concludes  that  determination  of 
the  germ  path  in  this  way  is  of  very  general  occurrence. 

In  many  insects  a  distinct  germinal  path  with  early  segregation 
of  the  primitive  germ  cells  has  been  observed.  Among  the  diptera 
all  forms  carefully  examined  show  some  sort  of  germ  path.  In  the 
gnat  Chironomus,  for  example  (Hasper,  'ii),  the  primitive  germ 
cell  is  segregated  in  the  second  cleavage  (Fig.  145),  and  in  the  fly 
Miastor  (Kahle,  '08;  Hegner,  '12,  '14a,  '14c)  the  segregation  of  the 
mother  germ  cell  occurs  in  the  third  cleavage,  one  nucleus  of  this 
cleavage  becoming  imbedded  in  a  pecuhar  cytoplasmic  region  at  the 
posterior  end  of  the  egg,  and  giving  rise  later  to  the  germ  cells, 
while  all  the  other  nuclei  undergo  a  process  of  diminution  of  chro- 
matin somewhat  similar  to  that  occurring  in  Ascaris. 

A  cytoplasmic  germ-path  determinant  in  the  form  of  a  peculiar 
granular  cytoplasmic  region  at  the  posterior  pole  of  the  egg,  which 
during  cleavage  becomes  nucleated  and  separates  off  as  the  primi- 
tive germ  cells,  has  recently  been  described  for  several  chrysomelid 
beetles,  including  the  potato  beetle,  by  Hegner  ('09,  '11,  '14a). 
This  author  concludes  with  Boveri  that  the  cytoplasm,  not  the 
nuclei,  determines  which  cells  shall  become  germ  cells,  but  this 


THE  GAMETES  IX  PLANTS  AND  AMM ALS 


329 


means  that  the  germ  cells  are  probably  determinerl  in  essentially 
the  same  way  as  other  parts  of  the  organism.  In  various  other 
insects  also  a  germ  path  has  been  described.  In  certain  hymcnop- 
tera  Hegner  ('146)  finds  that  the  granules  of  the  polar  cytoplasmic 
region  are  derived  from  the  disinte- 
grated nucleus  of  a  nutritive  cell  taken 
up  by  the  egg  during  its  growth,  an 
origin  very  similar  to  that  which 
Buchner  described  in  the  case  of  Sagitta. 

In  all  these  cases  among  the  inverte- 
brates the  factors  determining  what 
shall  become  germ  cells  and  what 
somatic  structures  apparently  exist  in 
the  cytoplasm  and  not  in  the  nuclei. 
Moreover,  the  cytoplasmic  regions 
which  determine  the  germ  cells  are  not 
directly  related  to  the  cytoplasm  of  pre- 
existing germ  cells,  but  very  evidently 
are  simply  regions  where  certain  special 
metabolic  conditions  exist.  Cells 
arising  from  these  regions  become  germ 
cells,  just  as  those  arising  from  other 
regions  become  one  part  or  another  of 
the  body.  It  is  of  interest  to  note  that 
very  generally  the  germ  cells  arise  from 
regions  of  the  egg  with  a  relatively  low 
metabolic  rate.  They  very  commonly 
divide  more  slowly  than  other  cells. 
In  fact,  it  seems  possible  that  this  low 
metabolic  rate,  rather  than  any  specific 
character,  determines  that  they  shall 
not  take  part  in  the  early  development 
of  the  body,  because  other  cells  react 

more  rapidly  than  they  do.     They  are,  so  to  speak,  left  behind 
and  only  later  become  an  active  functional  jxirt  of  the  organism. 

Among  the  vertebrates  comparatively  early  segregation  ol  the 
primitive  germ  cells  is  apparently  of  wide  occurrence  in  fishes. 


Fig.  145. — Early  cleavage  of 
Chironomiis,  a  gnat:  the  spindle 
at  the  lower  end  of  the  egg 
represents  the  primitive  germ 
cell;  the  cytoplasm  about  this 
spindle  separates  with  it  from 
the  remainder  of  the  egg  and 
divides  into  two  cells,  each  of 
which  divides  farther.  From 
llasper,  '11. 


330  SENESCENXE  AND  REJUVENESCENCE 

amphibia,  and  reptiles.  More  than  thirty  years  ago  Nussbaum 
('80)  described  the  early  differentiation  of  the  sex  cells  in  fishes 
and  amphibia.  Later,  Eigenmann  ('92,  '96a)  described  the  early 
segregation  of  germ  cells  in  fishes  and  found  that  the  primitive 
germ  cells  in  the  fish  Cymatogaster  were  segregated  in  the  fifth  cell 
generation  of  cleavage,  and  Wheeler  ('00)  found  a  relatively  early 
differentiation  of  the  germ  cells  in  the  lamprey.  Two  years  later 
Beard  ('02),  as  the  result  of  his  work  on  selachians,  reached  the 
conclusion  that  the  germ  cells  are  independent  unicellular  organisms 
which  pass  a  part  of  their  life  in  the  multicellular  sterile  soma. 
This  conclusion  rests  on  the  occurrence  in  embryonic  stages  of 
certain  large  cells  seen  by  various  investigators  in  certain  regions 
of  the  embryo  and  which  are  described  as  migrating  to  the  position 
of  the  sexual  organs  and  later  becoming  the  germ  cells.  Since 
Beard's  paper,  a  large  number  of  similar  observations  have  been 
made  by  various  authors  on  fishes,  amphibia,  and  reptiles. 

As  regards  all  these  data  on  germ-cell  segregation  in  the  verte- 
brates, the  first  question  is  the  correctness  of  the  observations. 
Much  time  has  been  devoted  to  the  observation  of  these  cells  in 
the  embryonic  stages  and  but  Httle  to  the  details  of  their  later  fate. 
Moreover,  the  extensive  migrations  described  from  various  regions 
of  the  embryo  to  the  position  of  the  sexual  organs  are  in  all  cases 
inferences  from  the  examination  of  fixed  and  stained  material. 
But  granting  that  the  observations  are  correct,  the  segregation  of 
the  germ  cells  is  no  earher  in  most  cases  than  that  of  many  other 
parts  of  the  body,  and  such  cases  afford  no  vahd  evidence  against 
the  view  that  the  germ  cells  are  integral,  specialized  parts  of 
the  body  like  other  organs.  In  most  cases  these  early  germ 
cells  in  vertebrates  are,  hke  those  of  invertebrates,  apparently 
cells  with  a  lower  rate  of  metabohsm  than  other  parts  of  the 
embryo.  Often  they  retain  yolk  granules  later  than  other  cells, 
and  in  all  respects  appear  to  be  less  active  during  early  stages 
(Eigenmann,  '966). 

At  present  the  only  conclusion  possible  from  all  these  observa- 
tions on  germ  paths  and  germinal  segregation  is  that  while  the  data, 
if  correct,  as  they  probably  are  in  at  least  many  cases,  do  indicate 
that  in  various  forms  the  germ  cells  become  more  or  less  distinctly 


THE  GAMETES  IN  PLANTS  AND  AMM ALS  331 

segregated  from  other  cells  at  early  stages  of  development,  they  do 
not  in  any  way  constitute  a  valid  argument  for  the  independence 
and  continuity  of  the  germ  plasm. 

Moreover,  there  are  many  animals  in  which  up  to  the  present 
time  no  indication  of  early  segregation  of  germ  cells  has  ever  been 
found  by  any  investigator.  In  some  of  these  forms,  e.g.,  certain 
fiatworms  and  the  polychete  annelids,  the  sex  organs  appear  only 
at  a  certain  stage  of  development,  or  periodically,  and  before  or 
between  the  periods  of  their  occurrence  no  traces  of  anything 
representing  germ  cells  can  be  found.  The  assumption  has  often 
been  made  that  in  such  cases  the  germ  plasm  is  segregated  in  cer- 
tain cells,  but  that  these  cells  possess  no  characteristic  visible  features 
distinguishing  them  from  other  cells  or  tissues.  In  the  turbellaria, 
for  example,  the  parenchyma  has  often  been  regarded  as  an  "in- 
different" tissue  representing  the  germ  plasm.  But  the  only 
justification  for  terming  such  tissues  as  the  turbellarian  parenchyma 
indifferent  or  undifferentiated  tissues  lies  in  the  fact  that  they  give 
rise  to  germ  cells  and  in  reconstitution  to  various  other  parts. 
Morphologically  they  are  not  undifferentiated,  but  possess  definite 
histological  characteristics  quite  different  from  those  of  cells  or 
tissues  which  are  really  embryonic  or  undifferentiated,  and  when 
other  tissues  or  organs  arise  from  them  they  first  lose  these  charac- 
teristics and  become  embryonic  and  then  undergo  a  new  differen- 
tiation. Moreover,  when  they  undergo  such  changes  their  rate  of 
metaboHsm  becomes  higher,  an  indication  that  they  are  undergoing 
dedifferentiation  and  becoming  younger.  They  may  be  less 
highly  specialized  than  certain  other  tissues  of  the  organism,  but 
only  theoretical  grounds  can  prevent  us  from  admitting  that  where 
the  germ  cells  arise  from  such  tissues  they  arise  from  dilTerentiated 
functional  parts  of  the  organism  by  a  process  of  dedilTerentiation 
and  redifferentiation. 

In  the  tapeworm  Moniezia,  for  example,  the  sex  cells  arise  from 
the  parenchyma,  and  apparently  any  parenchymal  cells  which  lie 
within  the  region  involved  in  the  production  of  sex  cells  may  undergo 
dedifferentiation  and  take  part  in  the  process.  Even  the  large 
muscle  cells  may  give  rise  to  testes,  as  indicated  in  Figs.  146  and  147. 
In  such  cases  the  muscle  fiber  undergoes  degeneration,  tlie  vacuoles 


332 


SENESCENCE  AND  REJUVENESCENCE 


disappear,  and  the  nucleus  begins  to  divide,  apparently  at  first 
amitotically. 

In  some  of  the  lower  animals  new  individuals  arise  agamically 
or  can  be  produced  by 
experimental  isolation  of 
pieces  from  regions  of  the 
body  which  do  not  contain 
sex  organs,  yet  these  indi- 
viduals are  capable  of  pro- 
ducing sex  cells.  To 
assume  that  these  regions 
of  the  body  contain  germ 
plasm  in  the  Weismannian 
sense  ready  to  develop  into 
ovaries  or  testes  when 
necessary  is  simply  to  beg 
the  question.  To  all 
appearances  germ  cells  de- 
velop in  such  cases  from 
more  or  less  differentiated 
cells  of  the  region  in- 
volved by  a  process  of 
dedifferentiation  and  re- 
differentiation,  and  the 
assumption  of  a  pre- 
existent  germ  plasm  is 
entirely  unnecessary. 

It  is  scarcely  probable 
that  the  germ  plasm  is  a 
totally  different  thing  in 
animals  and  plants.  In 
the  preceding  section  it 
has  been  pointed  out  that 
for  a  very  large  number  of 
plants  the  development  of 

germ  cells  from  differentiated  functional  cells  of  the  plant  body 
has  been  experimentally  demonstrated.     This  fact  in  itself  creates 


Figs.  146,  147. — Formation  of  a  testis  from  a 
muscle  cell  in  Moiiiczia:  Fig.  146,  large  muscle 
cell  with  single  fiber;  Fig.  147,  transformation 
of  muscle  cell  into  testis. 


THE  GAMETES  IX  PLANTS  ANT)  ANIMALS  333 

a  presumption  in  favor  of  a  similar  origin  in  animals,  and  the  pur- 
pose of  the  present  section  is  to  show  that  the  facts  themselves, 
when  correctly  analyzed,  point  to  the  same  conclusion.  The 
assumption  of  the  existence  of  supplementary  germ  plasm,  i.e.. 
of  portions  of  germ  plasm  in  the  nuclei  of  all  or  certain  somatic  cells 
or  tissues,  not  only  finds  no  support  in  the  data  of  observation  and 
experiment,  but  deprives  the  germ-plasm  hypothesis  of  all  scientific 
value.  It  is  undoubtedly  true  that  the  more  highly  specialized 
cells  of  an  organism,  be  it  animal  or  plant,  do  not  so  readily  undergo 
dedifferentiation  and  redifferentiation  under  altered  correlative 
conditions  and  so  do  not  so  readily  give  rise  to  germ  cells  or  other 
parts  as  do  the  less  highly  specialized  cells;  in  fact,  many  cells, 
especially  in  the  higher  forms,  are  probably  incapable  of  such 
change,  but  this  does  not  constitute  adequate  grounds  for  the  belief 
that  germ  plasm  and  soma  are  independent  entities. 

Summing  up,  it  appears  that  the  facts  afford  no  adequate 
grounds  for  regarding  the  germ  cells  as  anything  else  than  an 
integral  part  of  the  organism  specialized  in  a  certain  direction  like 
other  parts.  But  in  spite  of  the  complete  absence  of  any  trace  of 
early  segregation  of  germ  cells  in  many  organisms,  in  spite  of  the 
fact  that  the  egg  cytoplasm,  not  the  nucleus,  is  apparently  respon- 
sible in  most  if  not  in  all  cases  of  early  segregation,  in  spite  of  our 
ignorance  in  many  cases  whether  the  so-called  primitive  germ  cells 
really  give  rise  only  to  gametes,  and,  finally,  in  spite  of  the  remark- 
able conception  of  the  organic  world  to  which  the  germ-plasm 
theory  leads  us — in  spite  of  all  these  difficulties,  the  view  that  these 
processess  of  early  specialization  in  the  egg  constitute  a  spatial 
morphological  segregation  of  the  independent  germ  plasm  from  the 
body  or  soma  still  finds  supporters,  as  is  evident  from  the  most 
recent  consideration  of  the  subject  by  Hegner  ('14c). 

THE  MORPHOLOGICAL  CONDITION  OF  THE  G.^METES 

Minot  ('08)  has  maintained  on  morphological  grounds  that  the 
animal  egg  is  an  old  cell  approaching  death,  but  has  not.  so  far  as  I 
am  aware,  expressed  any  opinion  regarding  the  condition  ol  the 
spermatozoon,  although,  according  to  his  theory  that  increase  in 
the  proportion  of  cytoplasm  to  nuclear  substance  is  a  fundamental 


334  SENESCENCE  AND  REJUVENESCENCE 

factor  in  senescence,  the  spermatozoon  should  be  a  very  young  cell, 
for  it  is  almost  without  cytoplasm  in  most  cases.  I  have  called 
attention  to  various  lines  of  evidence  which  indicate  that  both  egg 
and  spermatozoon  are  highly  differentiated,  old  cells  (Child,  'ii), 
and  ConkHn  ('12,  '13)  has  expressed  himself  as  in  essential  agree- 
ment with  this  view. 

The  process  of  formation  of  the  gametes  in  its  morphological 
aspects  is  very  evidently  a  process  of  specialization  and  differentia- 
tion. The  fully  developed  gametic  cells  are  among  the  most  highly 
speciaHzed  cells,  if  not  the  most  highly  specialized  cells  of  the 
multicellular  organism,  but  the  primitive  germ  cells  from  which 
they  arise  are  minute  cells  without  any  morphological  structure 
beyond  that  common  to  cells  in  general,  and  with  a  high  metabolic 
rate — in  short,  with  all  the  visible  characteristics  of  embryonic  or 
unspeciaHzed,  undifferentiated  cells.  The  process  of  development 
of  the  gametes  from  such  cells  is  a  process  of  specialization  and 
morphological  differentiation  of  the  same  sort  as  that  which  occurs 
in  other  cells  of  the  organism.  Morphologically  the  fully  formed 
gamete  certainly  bears  no  resemblance  to  an  embryonic  cell.  A 
few  figures  will  serve  to  emphasize  this  point. 

In  Figs.  123-31  (pp.  317-18)  the  sex  organs  and  gametes  of  some 
of  the  algae  and  fungi  are  shown.  The  gametes  are  readily  dis- 
tinguished from  the  vegetative  cells  and  in  most  cases  appear  to  be 
more  highly  specialized  and  differentiated  than  those.  Male 
gametes,  the  spermatozoids  of  a  few  plants  from  other  groups,  are 
shown  in  Figs.  148-53.  Fig.  148  is  the  spermatozoid  of  a  liverwort; 
Fig.  149,  a  horse-tail,  Eguisetum;  Fig.  150,  a  fern;  Fig.  151,  a 
cycad,  Zamia;  Fig.  152  is  the  spermatozoid  or  generative  nucleus 
of  the  sunflower;  Fig.  140  (p.  320)  shows  the  pollen  grain  of  Sil- 
phium,  another  composite  with  the  two  elongated  generative  nuclei 
or  spermatozoids,  and  Fig.  153,  a  fully  developed  spermatozoid  of 
the  same  plant.  These  male  cells  are  different  in  various  ways, 
but  most  of  them  possess  a  well-developed  motor  apparatus  of  one 
kind  or  another. 

The  differentiation  of  the  male  gamete  among  the  animals  is 
perhaps  more  uniform  than  among  plants,  but  there  are  many 
animal  species  with  aberrant  forms  of  spermatozoa.     Figs.  154-57,, 


THE  GAMETES  IN  PLANTS  AND  ANIMALS 


335 


i6i,    and    i66    show    more    or    less    "typical,"    fully    developed 
spermatozoa  from  various  invertebrate  and  vertebrate  species,  and 


Figs.  148-153. — Male  gametes  of  various  plants:  Fig.  148,  Sphaerocarpus  Icr- 
restris,  a  liverwort  (from  Land,  unpublished);  Fig.  149,  Equisctum  (from  Sharp,  '12); 
Fig.  150,  Nephrodium,  a  fern  (from  Vamanouchi,  'oS);  Fig.  151,  Zamia,  a  cycad  (from 
Webber,  '01);  Fig.  152,  Ilclianllius,  sunflower  (from  Nawaschin,  00);  Fig.  153,  Sil- 
phium  (from  Merrell,  '00). 

in  Figs.  158-61  four  developmental  stages  of  the  guinea-pig  sperma- 
tozoon are  given.  A  few  of  the  aberrant  spermatozoan  forms 
among  animals  are  shown  in  Figs.  162-72.     Figs.  162-64  are  from 


33^ 


SENESCENCE  AND  REJUVENESCENCE 


three  species  of  turbellarian  worms,  forms  related  to  Planaria; 
Fig  165  is  the  non-motile  spermatozoon  of  the  nematode  worm 
Ascaris  megaloccphala;  Figs.  166  and  167  show  the  two  forms  of 
spermatozoa  found  in  certain  snails;  Figs.  168,  169,  and  170  are 


155 


154 


Figs.  154-157. — Male  gametes  of  various  animals:  Fig.  154,  Nereis, 
an  annelid  worm  (from  F.  R.  Lillie,  '12);  Fig.  155,  Copris,  a  beetle 
(from  Ballowitz,  'god);  Fig.  156,  Raja,  a  fish  (from  Ballowitz,  'gob); 
Fig.  157,  Triton,  a  salamander  (from  Ballowitz,  'go^). 


from  various  species  of  Crustacea,  and  Figs.  171  and  172  from 
arachnids,  but  Fig.  171  perhaps  represents  a  stage  of  spermatozoan 
development  rather  than  the  mature  form. 

Usually  the  male  gamete  in  both  plants  and  animals  is  highly 
motile,  and  the  course  of  its  development  is  to  a  large  extent  a 


THE  GAMETES  IX  TLAXTS  AND  AXIMALS 


337 


differentiation  of  the  motor  mechanism  from  a  cell  of  the  usual  sort. 
But  in  some  cases,  as  in  the  angiosperms  among  plants  (Figs.  152, 
153),  in  Ascaris  (Fig.  165),  and  in  the 
Crustacea  (Figs.  168-70)  among  animals, 
the  male  gamete  is  almost  or  quite  non- 
motile.  Even  in  such  cases,  however, 
it  is  none  the  less  a  highly  specialized 
cell.  In  the  angiosperms  among  plants 
a  morphologically  differentiated  cyto- 
plasmic mechanism  is  absent,  but  the 
history,  form,  and  behavior  of  the 
nucleus  attest  its  specialization.  In 
Ascaris  (Fig.  165)  the  peculiar  structure 
of  the  cell  shows  that  it  has  departed 
far  from  the  generalized  form  of  the 
embryonic  cell.  In  the  crustacean  sper- 
matozoa (Koltzoff,  'o6(z)  the  skeletal  or 
supporting  structures  are  extensively 
developed,  but  according  to  Koltzcff 
('o6i,  '08),  such  structures  are  present 
in  other  spermatozoa  also.  Ballowitz' 
('86-'o8)  extensive  studies  of  the  finer 
structure  of  the  spermatozoa  also 
demonstrate  the  morphological  com- 
plexity of  these  remarkable  cells.  In 
the  more  highly  differentiated  forms 
there  remains  no  trace  of  the  ordinary 
amorphous  cytoplasm  of  the  cells  from 
which  they  arise:  all  has  either  under- 
gone breakdown  as  a  source  of  energy 
or  has  been  transformed  into  the  fibrillar 
or  other  structures  of  the  spermatozoon. 
The  development  of  the  female 
gamete  follows  a  very  different  course, 
but  is  none  the  less  a  process  of  spe- 
cialization and  morphological  differen- 
tiation.    Figs.    123,  125,   126,  and  128 


Figs,  i 58-161. — Develop- 
ment of  spermatozoon  from 
spermatid  in  the  guinea-pig: 
rig.  15S,  beginning  of  trans- 
formation; Fig.  15Q,  beginning 
ofdevelopmentof  tail;  Fig.  i6o, 
side  view  after  formation  of 
the  thin  llat  head;  Fig.  161, 
mature  spermatozoon.  From 
Meves,  '99. 


33^ 


SENESCENCE  AND  REJUVENESCENCE 


(pp.  317-18)  show  the  female  gametes  in  some  of  the  algae  and 
fungi.     The  development  of  the  female  cell  in  the  liverwort  Riccia 


163 


164 


166 


167 


Figs.  162-167. — Some  peculiar  forms  of  spermatozoa  from  the  lower  inverte- 
brates: Fig.  162,  Plagiostomum,  a  turbellarian  (from  Bohmig,  '90);  Fig.  163,  Castroda, 
a  turbellarian  (from  Luther,  '04);  Fig.  164,  Mesostomiim,  a  turbellarian  (from  Luther, 
'04);  Fig.  16^,  Ascaris  megalocephala,  nematode  worm  (from  Scheben,  '05);  Figs.  166, 
167,  the  two  forms  of  spermatozoa  in  Paludiiia,  a  snail  (from  Meres,  '03). 


is  outlined  in  Figs.  133-39.    Fig.  173  shows  the  archegonium  of  the 
fern  Neplirodium,  containing  the  large  egg;  Fig.  174  is  the  fertilized 


THE  GAMETES  IN  PLANTS  AND  ANIMALS 


339 


egg  of  the  cycad  Zajnia;  Fig.  175,  the  archegonium  of  a  conifer, 
Torreya  taxifolia,  containing  the  large  egg:  incidentally  this  figure 
also  shows  the  pollen  tube 
with  the  two  small  male 
nuclei  near  the  tip.  The 
development  of  the  female 
gamete  in  the  angiospcrms 
isoutlined  in  Figs.  141,  A-E 
(p.  321).  Fig.  176  is  the 
embryo  sac  of  the  sun- 
flower at  the  time  of  ferti- 
lization, and  Fig.  177,  that 
of  the  conefiower,  another 
composite,  at  the  same 
stage.  The  eggs  in  all 
these  plants  are  manifestly 
highly  specialized  cells 
which  have  undergone 
great  changes  from  the 
embryonic   condition. 

The  animal  egg  usually 
exhibits  an  even  greater  de- 
gree of  morphological 
specialization  than  that  of 
the  plant  because  it  is 
loaded  to  a  greater  or  less 
degree  with  granules  or 
masses  of  yolk  substance 
which  becomes  available 
as  a  nutritive  supply  at 
the  beginning  of  embry- 
onic development.  The 
accumulation  of  yolk  is 
often  so  great  that  the  egg 
cell  attains  an  enormous 
size,  the  bird's  egg  representing  the  extreme  of  devclopnienl  in 
this  direction.     Since  the  period  of  growth  and  differentiation  of 


Figs.  168-172. — Peculiar  forms  of  sjxjrma- 
tozoa  from  the  arthroi)ods:  Figs.  16S,  169,  170, 
Pinnotheres,  Maja,  and  Miinidia,  all  Crustacea 
(from  Koltzofl,  '06a);  Figs.  171,  172,  Acanio- 
loplitis,  A  galena,  both  spiders  (from  Boscnbcrg, 
'05). 


340 


SENESCENCE  AND  REJUVENESCENCE 


the  animal  egg  as  a  single  cell  involves  so  much  more  extensive 
and  conspicuous  change  than  in  the  plant,  it  has  attracted  much 
attention  and  the  course  of  oogenesis  has  been  described  for  many 
animal  species.  The  following  figures  include  characteristic  stages 
in  the  differentiation  of  a  few  animal  eggs.  Figs.  178-80  show 
the  egg  of  the  fresh-water  hydra,  first  at  the  beginning  of  its 
growth  as  a  small  cell  lying  between  the  cells  of  the  ectoderm 
(Fig.    178);    secondly,    as   a   large   amoeboid   cell   in    the   ovary 

(Fig.  179);  and,  thirdly, 
as  a  full-grown  egg,  still 
in  the  ovary,  with  large 
yolk  spheres  in  the 
cytoplasm.  Figs.  181 
and  182  show  the  primi- 
tive germ  cells  and  the 
final  stage  of  oogenesis 
in  the  liver  ^ukeFasciola 
hepatica,  a  parasitic  flat- 


worm.     In  most  of  the 


flatworms     the 


e  a  cr 


Figs.  173-174. — Fig.  173,  archegonium  of  Nepliro- 
diiun,  a  fern,  containing  the  egg,  0  (from  Yama- 
nouchi,  '08);  Fig.  174,  fertilized  egg  of  Zamia, 
a  cycad  (from  Webber,  '01). 


accumulates  little  or  no 
yolk  within  its  own 
cytoplasm,  but  other 
nutritive  cells  contain- 
ing yolk  are  inclosed  in 
the  capsule  with  it  be- 
fore it  is  extruded.  In 
these  forms  the  egg  cell 
itself  remains  of  small 
size  and  its  growth  history  is  relatively  simple.  In  this  and  in 
various  other  animals  the  egg  as  it  grows  develops  a  stalk  (Fig.  182) 
by  which  it  is  connected  with  the  ovarian  wall  and  through  which 
it  probably  receives  most  or  all  of  its  nutrition.  Fig.  183  shows 
an  ovary  of  the  bryozoan  Plumatella  fimgosa,  with  eggs  in  various 
stages  of  growth  and  differentiation.  These  eggs  develop  succes- 
sively from  the  primitive  cells,  and  each  egg  in  turn  is  displaced 
by  the  growth  of  another  behind  it. 


THE   GAMETES  L\  PLANTS  AND  AM.MALS 


341 


The  interesting  oogenesis  of  Stcr}iaspis  scutala,  a  peculiar  marine 
annelid,  is  shown  in  Figs.  184  and  185.  The  eggs  arise  from  cells 
on  the  walls  of  certain  blood  vessels  and  as  they  grow  develop  a 
stalk  containing  a  loop  of  the  blood  vessel,  so  that  blood  flows 
directly  through  the 
basal  end  of  the  egg. 
Fig.  184  shows  the  egg 
at  the  beginning  of  yolk 
formation:  the  cyto- 
plasm contains  a  few 
yolk  granules  and  shows 
a  strongly  radiate 
structure  centering 
about  the  vascular  loop. 
In  the  full-grown  egg 
the  cytoplasm  is  loaded 


with  numerous  large 
yolk  spheres  (Fig.  185) 
except  at  the  basal  end, 
where  there  is  an  area 
of  granular  cytoplasm. 
At  this  stage  the  egg 
becomes  free  from  the 
stalk,  which  undergoes 
atrophy  and  resorption. 

A  different  type  of 
oogenesis  is  shown  in 
Fig.  186,  an  ovarian 
tubule  from  the  water 
beetle  Dytiscus  margi- 
nalis.     Here    growing 

eggs  alternate  with  groups  of  so-called  nurse  cells,  which  serve  as  a 
food  supply  and  are  used  up  during  the  growth  of  the  egg. 

Three  stages  of  ascidian  oogenesis  are  shown  in  Figs.  187-S9. 
The  first,  the  young  ovotestis,  the  animals  being  hermaphroditic, 
with  a  young  egg  cell  at  the  left,  the  second,  the  growing  egg  sur- 
rounded by  its  follicle  from  which  the  so-called  test  cells — cells 


Fig.  175. — Female  gametophyte  of  Torrrya,  a 
conifer,  showing  the  egg,  0,  and  above  it  the  pollen 
tube  with  the  two  male  nuclei,  sp.  From  Coulter 
and  Land,  '05. 


342 


SENESCENCE  AND  REJUVENESCENCE 


which  enter  the  cytoplasm  of  the  egg  and  serve  as  food — -are  begin- 
ning to  arise.  The  third  figure  (Fig.  189)  shows  a  segment  of  the 
egg  at  a  still  later  stage  with  folhcle  and  test  cells  in  the  peripheral 
cytoplasm  and  yolk  masses  forming  below  them.     Figs.  190,  191 


Figs.  176,  177. — Embryo  sacs  of  Hdianthus  (sunflower)  and  Rudbcckia  (cone- 
flower)  at  time  of  fertilization,  showing  egg,  0;  two  male  nuclei,  spi,  spi',  embryo  sac 
nucleus,  en.     From  Nawaschin,  '00. 

are  two  stages  in  the  oogenesis  of  a  fish  egg,  the  first  showing  the 
young  egg  at  the  beginning  of  yolk  formation,  the  second,  a  later 
stage  in  which  the  cytoplasm  is  loaded  with  numerous  yolk  spheres. 
In  various  invertebrate  groups  the  same  individuals  produce  at 
different  times  parthenogenic  eggs,  i.e.,  eggs  which  develop  without 


THE  GAMETES  IX  PLANTS  AXD  AXIMALS 


343 


fertilization,  and  zygogenic  eggs  which  require  fertilization  before 
development.  It  is  a  fact  of  great  interest  that  in  such  cases  the 
parthenogenic  eggs  usually  dilTer  morphologically  from  the  zygo- 
genic eggs.  In  Sida  crystallina,  one  of  the  cladoceran  Crustacea,  for 
example,  the  parthenogenic  eggs  are  smaller  and  contain  less  yolk 


Figs.  178-180. — Three 
stages  in  the  differentiation 
of  the  egg,  0,  of  Hydra. 
From  Downing,  '09. 


than  the  zygogenic  eggs.  Fig.  192  shows  an  ovarian  tubule  of  this 
species  containing  various  stages  of  parthenogenic  oogenesis.  The 
primitive  cells  {pc),  formed  at  the  upper  end  of  the  tubule,  after 
the  period  of  division  is  over  arrange  themselves  in  groups  of  four 
{gi  g)  of  which   the   third   from  the  upper  end  develops  into  an 


344 


SENESCENCE  AND  REJUVENESCENCE 


18? 


egg  (o)  and  the  other  three  become  nurse  cells,  which  supply  the  egg 
with  nutrition.  Three  of  these  nurse  cells  thus  contribute  to  the 
formation  of  one  parthenogenic  egg.  The  zygogenic  egg,  however, 
uses  up  not  only  three  nutritive  cells,  but  often  several  other  cell 
groups,  including  the  young  egg  cells,  i.e.,  a  much  larger  amount  of 
nutritive  material  contributes  to  its  formation  than  to  that  of  the 
parthenogenic  egg.     Fig.  193  shows  the  lower  end  of  an  ovarian 

tubule  containing  a  zygogenic  egg. 
It  is  much  larger  than  the  par- 
thenogenic egg  and  contains  more 
yolk. 

Among  the  insects,  the  plant 
lice  also  produce  both  partheno- 
genic and  zygogenic  eggs.  In  this 
case  the  difference  between  the 
two  kinds  of  eggs  is  very  marked, 
the  parthenogenic  egg  being  much 
the  smaller  and  containing  little 
yolk  (Fig.  194)  as  compared  with 
the  zygogenic  egg  (Fig.  195). 
Even  the  nurse  cells,  which  here 
form  a  sort  of  gland  with  which 
the  egg  cell  is  connected  by  a  pro- 
toplasmic strand,  are  larger  and 
more  highly  developed  in  the  latter 
case.  Similar  differences  have 
been  observed  in  other  forms  pro- 
ducing the  two  kinds  of  eggs.  If 
the  process  of  oogenesis  is  a  pro- 
cess of  differentiation  and  senescence,  we  must  conclude  that  in  these 
cases  the  parthenogenic  egg  does  not  proceed  so  far  in  development 
as  the  zygogenic  egg.  Morphologically  it  is  evidently  less  highly 
differentiated  and  younger. 

Among  the  bees,  however,  where  eggs  which  produce  males, 
i.e.,  the  drones,  apparently  develop  parthenogenically,  while  the 
females,  both  workers  and  queens,  develop  from  fertilized  eggs,  no 
characteristic   morphological   differences   between    the   partheno- 


i 


Figs.  181,  182. — Primitive  germ 
cells  and  full-grown  egg  of  Fasciola 
(liver  fluke),  with  stalk  of  attachment. 
From  Schubmann,  '05. 


THE  GAMETES  IN  PLANTS  AND  AMMALS  345 

genie,  male-producing,  and  the  zygogenic,  female-producing,  eggs 
have,  so  far  as  I  am  aware,  been  described.  But  the  morph(;logical 
differences  in  the  daphnids  and  plant  lice  are  evidently  extreme, 


Figs.  183-185.— Fig.  183,  ovary 
of  PlumatcUa  (bryozoan),  showinj,' 
eggs  in  various  stages  of  growth 
and  dififerentiation.  From  Braem, 
'97;  Figs.  184,  185,  growing  egg 
of  Stcrnaspis  (annelid),  attached 
to  a  stalk  which  contains  a  vas- 
cular loop;   full-grown  egg. 


and  it  is  possible  either  that  much  less  conspicuous  morphological 
differences  e.xist  in  the  bees,  or  that  the  physiological  differences 
are  so  slight  as   to   be  morphologically  inappreciable;   probably 


346 


SEXESCENXE  AND  REJUVENESCENCE 


Fig.  i86.— Part  of  an  ovarian 
tubule  of  Dytiscus  (beetle),  show- 
ing eggs  alternating  with  groups  of 
nutritive  cells:  the  dark  regions  of 
the  eggs  are  dense  aggregations  of 
granules  derived  from  the  nutritive 
cells.     From  Korschelt,  '91. 


the  physiological  condition  of  the 
bee's  egg  is  so  near  the  boundary 
line  between  parthenogenesis  and 
zygogenesis  that  slight  differences 
suffice  to  determine  it  one  way  or 
the  other. 

Many  other  interesting  cases  of 
oogenesis  might  be  added  to  the  few 
described  here,  but  the  fact  that  the 
formation  of  the  female  gamete  in 
organisms  is  a  process  of  growth  and 
morphological  dift'erentiation  requires 
no  further  evidence. 

The  gametes  then  in  both  plants 
and  animals  are  to  all  appearances 
the  final  stages  of  a  period  of  growth 
and  differentiation.     Except  in  a  few 
of   the   unicellular   organisms   where 
body  and  gamete  are  the  same  cell, 
the   gametes   are   highly    specialized 
cells,  different  from  any  other  cells 
of    the    body    and    bearing  not   the 
slightest   resemblance   to   embryonic 
or  undift'erentiated  cells.     Of  course 
it  is  possible  to  assume  with  Weis- 
mann  and  others   that,  in   addition 
to    the   oogenic    and    spermatogenic 
protoplasm  which  is  responsible  for 
the  differentiation,  the  cells  each  con- 
tain "undift'erentiated  germ  plasm," 
but    we    can    find    neither    morpho- 
logical nor  physico-chemical  support 
for  such  an  assumption.     Not  only 
is  such  germ  plasm  not  visible,  but 
from    a    physico-chemical    point    of 
view  it  is  difficult  to  conceive  how  it 
could  continue  to  exist  through  the 
course  of  differentiation  of  the 


THE  GAMETES  L\   I'LAM  S  ANO  AMMAL.^ 


o47 


gametic  cells.  The  only  conclusion  in  agreement  with  the  facts 
is  that  the  gametes  are  physiologically  integral  j)arts  of  the 
organism,  that  they  are,  like  other  parts  of  the  organism,  more  or 


Figs.  187-191. — Oogenesis  of  ascidian  and  fish:  Fig.  1S7,  ovotestis  of  young  bud 
of  DistapUa  (ascidian)  with  primitive  egg  cell,  0;  Fig.  18S,  growing  egg  with  test 
cells  and  follicle;  Fig.  189,  portion  of  half-grown  egg,  showing  follicle,  test  cells,  and 
formation  of  yolk  (from  Bancroft,  '99);  Figs.  190,  191,  Two  stages  in  the  growth 
and  differentiation  of  the  egg  of  Rhombus  (fish)  (from  Cunningham,  '97). 


less  highly  differentiated  cells,  and  that,  like  other  parts,  they 
undergo  differentiation  because  of  the  conditions  to  which  they 
are  subjected  in  the  organism  and  not  because  of  peculiar,  inherent 
properties. 


348 


SENESCENCE  AND  REJUVENESCENCE 


Figs.  192-195. — -The  differentiation  of  parthenogenic  and  z\'gogenic  eggs:  Fig. 
192,  ovarian  tubule  of  Sida  (daphnid  crustacean),  showing  primitive  germ  cells,  pc, 
and  groups,  g  g,  of  eggs,  0,  and  nurse  cells;  Fig.  193,  part  of  a  tubule  containing  a 
zygogenic  egg,  0;  Fig.  194,  ovarian  tubule  of  Melanoxanthiim  (plant  louse),  showing 
nutritive  gland,  0  gl,  parthenogenic  egg,  0,  and  embryo,  em;  Fig.  195,  ovarian  tubule 
of  Melanoxanthiim,  showing  nutritive  gland,  0  gl,  and  zygogenic  egg,  0.  Figs.  192,  193, 
from  Weismann,  '77;  Figs.  194,  195,  from  Tannreuther,  '07. 


THE  GAMETES  L\   I'LAMS  AND  ANIMALS  349 

THE  PHYSIOLOGICAL  CONDITION  OF  THE  GAMETES 

If  the  gametes  are  highly  differentiated  cells— the  final  stages  of 
a  period  of  growth  and  progressive  de\'elopment— they  must  be 
physiologically  in  an  advanced  stage  of  senescence.  Their  rate  vi 
metabolism  and  rate  of  growth  must  have  been  high  at  the  beginning 
of  the  period  of  differentiation  and  have  undergone  decrease  during 
this  period. 

As  regards  these  points,  our  positive  experimental  knowledge 
is  very  slight,  but  various  facts  of  observation  point  very  clearly 
to  certain  conclusions.  Growth  has  ceased  in  the  fully  developed 
gametes,  but  the  earlier  stages  of  their  development  are  periods  of 
rapid  and  extensive  growth,  and  in  the  plants  there  is  usually  more 
or  less  cell  division  in  the  earlier  stages  of  gametic  development. 
In  the  female  gamete  growth  is  usually  considerable,  often  very 
great  in  amount.  In  many  of  the  lower  plants  the  cytoplasm  of 
the  egg  becomes  loaded  with  nutritive  substance,  as  in  the  case  of 
the  yolk-bearing  animal  egg,  but  in  the  higher  plants  development 
follows  a  different  course  and  the  embryo  obtains  its  food  to  a  large 
extent  from  other  cells.  The  rate  of  growth  in  the  developing 
gamete  is  apparently  higher  in  the  earlier  than  in  the  later  stages, 
but  I  am  unable  to  cite  any  exact  observations  upon  this  point. 

The  course  of  development  in  the  male  gamete  usually  dilTers 
very  widely  from  that  in  the  female.  Growth  occurs,  but  it  is  much 
less  in  amount,  and  instead  of  the  accumulation  of  inactive  sub- 
stance in  the  cytoplasm,  a  transformation  of  the  cytoplasm  into  a 
morphological  mechanism,  usually  motor  in  function,  occurs.  In 
the  fully  developed  male  gamete,  as  in  the  female,  growth  has 
ceased.  In  most  cases  the  general  metabolic  substratum  of  the 
cell  has  to  a  large  extent  or  wholly  disappeared  and  the  cell  has  very 
evidently  progressed  as  far  as  is  possible  in  a  certain  direction. 

As  regards  the  metabolic  condition  of  the  gametes  of  plants. 
G.  Maige  ('09,  '11)  has  shown  that  the  rate  of  respiration  decreases 
in  the  anther  during  the  development  of  the  pollen  grain  from  the 
spore.  The  rate  of  respiration  in  the  pistil,  however,  is  usually 
higher  than  in  the  anther  and  frequently  increases  during  the 
development  of  this  organ.  The  changes  of  rate  in  the  embryo  sac 
alone  have  not  been  determined,  but  it  seems  prob.-ible  that  the 


350  SENESCENCE  AND  REJUVENESCENCE 

high  rate  and  the  increase  in  rate  in  the  pistil  as  a  whole  are  asso- 
ciated with  the  reproductive  processes  concerned  in  the  formation 
of  the  ovules  and  embryo  sacs  within  them,  processes  which  involve 
much  more  extensive  growth  than  the  development  of  the  pollen 
grain.  The  volume  and  weight  of  these  parts  in  relation  to  total 
volume  and  weight  of  the  pistil  increases  as  development  goes  on, 
and  this  change  is  undoubtedly  sufficient  to  account  for  the  increase 
in  respiratory  rate  in  the  whole  pistil  in  those  cases  where  it  occurs. 
Probably  the  rate  of  respiration  in  the  embryo  sac  decreases  as  its 
development  proceeds.  Fertilization  occurs  and  embryonic  devel- 
opment begins  in  the  seed  plants  without  any  considerable  period 
of  rest,  and  this  fact  may  also  play  a  part  in  determining  a  high 
respiratory  rate  in  the  pistil  during  the  later  stages  of  its  existence. 
Determinations  of  the  rate  of  oxygen  consumption  or  production 
of  carbon  dioxide  or  other  metabolic  products  have  not  been  made 
for  different  stages  of  gametic  development  in  animals,  but  as 
regards  the  egg  there  can  be  little  doubt  that  the  rate  of  metabolism 
decreases  as  development  proceeds  and  that  in  the  fully  developed 
egg  very  little  chemical  activity  is  going  on.  The  male  gamete,  on 
the  other  hand,  usually  shows  very  great  motor  activity,  often  con- 
tinuing over  a  long  period  of  time,  and  at  first  glance  there  may 
seem  to  be  little  reason  for  regarding  it  as  a  physiologically  old, 
highly  specialized  cell,  approaching  death.  It  must  be  remem- 
bered, however,  that,  except  in  some  of  the  less  highly  differentiated 
male  cells  of  the  unicellular  organisms  and  the  lower  plants,  the 
motor  activity  of  the  sperm  is  wholly  or  in  large  degree  due  to 
external  stimulation.  In  this  respect  the  sperm  resembles  volun- 
tary muscle.  In  both  cases  the  fully  differentiated  cell  or  tissue  is 
capable,  when  stimulated,  of  a  very  high  rate  of  reaction,  perhaps 
higher  than  that  in  the  sperm  mother  cell  or  the  embryonic  muscle 
cell,  but  it  is  certain  that  the  self-determined  inherent  rate  of  meta- 
bolic change  without  stimulation  in  the  differentiated  cell  is  a  much 
more  exact  measure  of  its  physiological  condition  or  its  stage  of 
senescence  as  compared  with  the  embryonic  cell.  In  the  "resting" 
muscle  and  in  the  motionless  spermatozoon  the  metabolic  rate  is 
undoubtedly  lower  than  in  the  undifferentiated  cells  from  which 
they  arose. 


THE  GAMKTES  IX  TL.WTS  WD  AXIM  \LS  351 

It  is  a  question  of  some  interest  wheliier  ihe  ener|,'y  expended 
in  the  movements  of  the  spermatozoon  is  derived  entirely  from  its 
own  substance  or  whether  in  any  case  it  obtains  nutritive  material 
from  the  fluids  in  which  its  movement  occurs.  It  is  ditVicult  to 
understand  how  some  of  the  more  highly  speciaHzed  forms  of 
animal  spermatozoa  can  contain  a  suft'icient  amount  (jf  material  to 
furnish  energy  for  their  long-continued  activit}-.  If  the  sj^erma- 
tozoon  does  obtain  nutrition  from  the  external  world  after  its 
isolation  from  the  parent  body,  it  may  perhaps  undergo  some 
degree  of  senescence  even  during  this  period. 

Tests  of  the  susceptibility  to  cyanide  of  various  developmental 
stages  of  the  gametes  have  given  uniform  results.     Thus  far  I  have 
made  susceptibihty  tests  on  the  female  cells  of  the  starfish  and  sea- 
urchin,  of  various  marine  annelids,  and  of  the  hsh  Tautogoldbrus. 
and  upon  both  female  and  male  cells  of  the  nematode  worm  A  scar  is 
mcgalocephala.     Ascaris  is  a  particularly  favorable  form  for  tests 
of  this  sort,  first,  because  ovaries  and  testes  are  tubular  organs 
lying  in  the  body  cavity  and  can  readily  be  removed;    secondl\-. 
because  all  stages  in  the  development  of  the  male  and  female 
gametes  can  be  obtained  from  a  single  individual  of  the  proper  sex 
at  any  time;  and,  thirdly,  because  the  spermatozoa  are  non-motile. 
In  both  male  and  female  the  primitive  mother  cells  in  the  uppermost 
or  innermost  portion  of  the  tubular  testis  or  ovary,  where  growth 
and  cell  division  are  still  occurring,  show  very  high  susceptibilitv 
hke  that  of  embryonic  cells;    lower  down  in  the  tube,  where  the 
growth  and  development  of  the  gametes  begin,  the  susceptibility 
begins  to  decrease,  and  the  decrease  is  progressive  as  gametic  devel- 
opment proceeds,  until  in  the  fully  developed  gamete  the  suscejJti- 
bility  is  exceedingly  low.     In  a  potassium  cyanide  solution,  0.005 
mol.,  the  primitive  female  mother  cells  underwent  the  death  change 
and  disintegrated  almost  at  once,  the  earlier  stages  of  the  growth 
period  in  fifteen  to  thirty  minutes,  somewhat  later  stages  in  one  to 
two  hours,  while  the  full}'  formed  eggs  showed  in  most  cases  no 
changes  until  after  twenty-four  to  forty-eight  hours  in  the  .solution 
and  did  not  actually  disintegrate  for  several  days.     Numerous  other 
stages  were  tested,  and  in  all  cases  the  susceptibility  was  found  to 
undergo  a  progressive  decrease.     The  male  cells  show  essentially 


352  SENESCENCE  AND  REJUVENESCENCE 

the  same  progressive  change  in  susceptibihty,  although  it  is  very 
difficult  to  determine  with  certainty  when  death  occurs  in  the 
mature  spermatozoon. 

In  the  other  forms  examined  attention  has  been  directed  chiefly 
to  the  female  cells,  because  the  different  stages  of  development  are 
readily  distinguishable  by  size  and  because  in  the  male  the  cells  are 
minute,  the  different  stages  being  in  most  cases  less  readily  dis- 
tinguishable in  the  living  cells,  except  under  very  high  powers,  and 
finally  the  spermatozoa  are  motile  and  it  is  practically  impossible 
to  eliminate  the  motor  activity  without  injuring  the  sperm  or 
altering  its  physiological  condition.  In  all  cases  where  female 
cells  were  examined  the  results  are  similar  to  those  with  Ascaris 
cells.  The  susceptibility  of  the  primitive  mother  cells  is  high, 
approaching  that  of  embryonic  cells,  and  decreases  progressively 
during  development  of  the  gamete,  and  that  of  the  full-grown  egg 
is  exceedingly  low — -lower  than  that  of  most  differentiated  cells. 
Wherever  the  stages  of  spermatogenesis  could  be  clearly  distin- 
guished the  same  results  have  been  obtained  for  the  non-motile 
stages. 

The  susceptibihty  to  cyanide  of  conjugating  infusoria  (Colpid- 
ium)  is  very  distinctly  lower  than  that  of  non-conjugating  and  divid- 
ing stages  (see  p.  381).  The  conjugating  stages  in  these  animals 
are  comparable  to  the  fully  developed  gametes  of  multicellular 
forms,  and  their  low  susceptibihty  indicates  that  their  rate  of 
metabohsm  is  lower  and  they  are  physiologically  older  than  other 
stages. 

If  the  susceptibility  method  can  be  trusted,  and  a  large  and 
increasing  volume  of  evidence  indicates  that  it  can,  the  development 
of  the  gametes  in  animals  is  associated,  as  the  decrease  in  suscep- 
tibility indicates,  with  a  decrease  in  rate  of  metabolism — a  process 
of  senescence — and  the  fully  developed  gamete  is  physiologically 
an  old  cell  approaching  death. 

Chemical  analysis  of  heads  of  spermatozoa,'  so  far  as  it  throws 
any  light  on  the  question,  indicates  that  at  least  some  spermatozoa 

'  The  literature  of  the  subject,  including  the  pioneer  work  of  ]\Iiescher  and  A.  P. 
Mathews'  analyses  (Alathews,  '97),  is  discussed  by  Burian,  '04,  '06.  Recently 
Steudel  ('iia,  'iib,  '13)  has  made  new  analyses  with  improved  methods. 


THE  GAMETES  IX  TLAXTS  AXD  AXI.MALS  353 

are  highly  specialized  and  that  this  specialization  has  been  in  the 
direction  of  a  chemical  simplification,  at  least  during  the  later 
stages.  Apparently  the  proteid  constituents  may  undergo  more 
or  less  breakdown  during  spermatogenesis.  According  to  Burian, 
this  process  of  breakdown  of  the  proteid  constituents  may  differ  in 
degree  in  different  spermatozoa.  So  far  as  our  knowledge  goes, 
the  spermatozoa  of  vertebrates,  except  the  fishes,  contain  typical 
proteids  as  constituents  of  their  nucleoproteids,  while  in  the  fishes 
these  are  replaced  by  the  simpler  histones  or  the  still  simpler 
protamines,  and  in  some  cases  the  histones  are  formed  during 
spermatogenesis,  the  protamines  in  the  fully  developed  sperma- 
tozoa. The  nucleoproteids  of  the  nuclei  of  other  cells  of  the  body 
sometimes  contain  typical  proteids,  sometimes  histones,  in  com- 
bination with  the  nucleic  acid,  but  the  process  of  proteid  breakdown 
does  not  go  as  far  as  the  formation  of  protamines.  From  this  point 
of  view,  the  differentiation  of  spermatozoa  is  apparently  not  funda- 
mentally different  from  that  of  other  cells,  but  some  spermatozoa 
seem  to  be  more  highly  specialized  than  other  cells. 

As  regards  the  eggs,  it  is  evident  that,  at  least  in  those  cases 
where  they  contain  yolk,  a  progressive  change  in  chemical  consti- 
tution of  the  whole  cell  must  occur  during  the  course  of  dilTerentia- 
tion:  the  most  striking  feature  of  this  change  is  the  increase  in 
lipoids,  which  form  an  important  constituent  of  the  yolk.  Con- 
cerning changes  in  chemical  constitution  of  the  egg  nucleus  we  know 
practically  nothing. 

THE  SIGNIFICANCE  OF  MATURATION 

At  some  point  in  the  life  history  between  successive  generations 
of  gametes  the  process  known  as  maturation  occurs.  In  most 
cases,  both  in  animals  and  in  plants,  the  process  of  maturation 
consists  of  two  nuclear  and  cell  divisions  during  which  the  number 
of  chromosomes  in  the  nucleus  is  decreased  one-half  more  or  less 
(haploid  number).  In  fertilization  the  normal  or  dipU)i(l  number 
is  restored  by  the  union  of  the  two  gametes  each  with  the  haploid 
number.  In  spite  of  years  of  investigation  and  discussion,  cytolo- 
gists  appear  to  be  almost  as  far  as  ever  from  an  agreement  as  to 
what  really  occurs  in  the  maturation  divisions;   indeed,  it  is  still  a 


354  SENESCENCE  AND  REJUVENESCENCE 

question  whether  the  maturation  divisions  or  either  one  of  them 
are  in  any  way  fundamentally  different  from  other  nuclear  divi- 
sions. They  are  beheved  by  many  to  be  of  great  importance  in 
heredity,  but  until  the  problem  of  their  cytological  character  is 
solved  any  consideration  of  their  significance  for  heredity  must 
remain  in  the  field  of  speculation. 

The  question  of  the  physiological  significance  of  maturation  has 
attracted  little  attention,  but  as  a  matter  of  fact  it  is  in  the  answer 
to  this  question  that  we  shall  find  the  key  for  the  solution  of  the 
other  problems  which  have  arisen  in  connection  with  maturation. 
At  least  one  of  the  maturation  divisions,  the  so-called  heterotypic 
division — but  whether  the  first  or  the  second,  opinions  differ — has 
commonly  been  supposed  to  be  distinguished  from  ordinary  divi- 
sions by  the  behavior  of  the  chromosomes,  and  much  has  been  made 
in  a  theoretical  way  of  this  difference.  But  with  the  extension  of 
our  knowledge,  one  feature  after  another  which  was  believed  to  be 
characteristic  of  the  maturation  division  has  been  found  in  other 
divisions  which  have  nothing  to  do  with  the  development  of  the 
gametes.  The  peculiar  behavior  of  the  chromatin,  consisting  in 
premature  division  and  agglutination  of  chromosomes  to  form  rings 
or  other  figures,  which  has  been  regarded  as  a  characteristic  feature 
of  the  so-called  "heterotypic"  maturation  division,  has  been 
observed  by  Hacker,  Bonnevie,  and  others  in  cleavage  stages  of 
various  forms,  has  also  been  found  in  the  cells  of  mahgnant  tumors, 
and  has  been  experimentally  induced  by  the  use  of  ether  and  chloro- 
form and  as  a  result  of  injury  to  the  parent  body.'  Hacker  is 
inchned  to  believe  that  this  heterotypic  behavior  of  the  chro- 
mosomes indicates  a  low  degree  of  differentiation,  hence  its  occur- 
rence in  gametic  history,  in  early  cleavage,  and  in  cancer  cells 
which  are  often  regarded  as  a  product  of  dedifferentiation.  Hacker 
was  led  to  this  conclusion  by  his  behef ,  based  on  theoretical  grounds, 
that  the  gametes  are  undifferentiated  cells  containing  germ  plasm, 
but  from  a  physiological  point  of  view  both  the  stages  in  gametic 
history  where  maturation  occurs  and  the  early  cleavage  stages  are 
stages  of  relatively  high  dift'erentiation. 

I  Bonnevie,  '08;  Farmer,  Moore,  and  Walker,  '04;  Hacker,  '00,  '04,  '07; 
Schiller,  '09. 


THE  GAMETES  IN  PLANTS  AM)  AMMALS  355 

It  is  evident  that  whatever  the  cytological  or  hereditary  signifi- 
cance of  the  chromosome  behavior  in  maturation,  this  behavior 
must  have  a  physiological  basis,  it  must  be  associated  with  certain 
physiological  conditions.  The  discovery  of  similar  behavior  in 
other  cells  and  the  experimental  production  of  it  serve  at  least  to 
pave  the  way  for  the  determination  of  its  physiological  significance. 
The  fact  that  the  "heterotypic"  behavior  can  be  experimentally 
induced  by  means  of  narcotics  seems  to  show  that  its  occurrence 
is  connected  with  a  low  rate  of  metabolism.  In  maturation,  both 
in  plants  and  in  animals,  it  occurs  at  the  end  of  a  developmental 
period.  In  most  plants  with  alternation  of  generations  the  matura- 
tion divisions  occur  in  the  formation  of  the  spores,  and  a  more  or 
less  extended  period  of  dedifferentiation,  cell  division,  and  pro- 
gressive development,  i.e.,  the  gametophyte  generation,  occurs 
between  maturation  and  fertilization.  In  animals,  on  the  other 
hand,  no  cell  division  occurs  between  maturation  and  fertilization. 
But  the  important  point  is  that  in  all  cases  the  maturation  divisions 
occur  in  cells  which  are  in  an  advanced  stage  of  developmental 
history  and  physiologically  old  and  which  therefore  possess  a  low 
metabolic  rate.  The  occurrence  of  heterotypic  behavior  in  cancer 
cells  is  probably  likewise  due  to  a  low  metabolic  rate,  though  not 
in  consequence  of  differentiation  and  advanced  age,  but  because 
of  partial  asphyxiation  or  intoxication  of  certain  cells  in  the  rapidly 
growing  cell  mass. 

According  to  this  conception,  then,  the  peculiar  characteristics 
of  the  maturation  divisions  find  their  physiological  basis  in  a  low 
metabolic  rate  which  may  result  from  differentiation  and  senescence 
or  be  induced  experimentally  or  otherwise.  Other  features  of 
maturation  which  indicate  a  low  metabolic  rate  are  the  absence 
of  the  usual  nuclear  growth  between  the  first  and  second  divisions 
and,  in  animal  eggs,  the  slow  progress  of  maturation  and  its  frequent 
cessation  until  a  further  stimulation  from  without  occurs,  and  the 
very  slight  influence  of  the  nuclear  division  upon  the  cytoplasm,  the 
cytoplasmic  divisions  resulting  in  the  formation  of  the  minute  iK)lar 
bodies  and  leaving  practically  the  whole  volume  of  the  egg  intact. 

In  the  animal  egg,  where  maturation  occurs  after  the  enormous 
growth  of  the  egg  cell  is  completed,  the  process  appears  to  be 


356  SENESCENCE  AND  REJUVENESCENCE 

initiated  either  by  the  physiological  or  physical  isolation  of  the  egg 
cell  from  its  source  of  nutritive  supply  in  the  parent  body,  or  often 
by  its  extrusion  from  the  body  into  water,  or  in  many  cases  only 
after  the  spermatozoon  has  entered  the  egg.  In  most  cases  the  egg  is 
incapable  of  even  the  maturation  divisions,  except  after  some  degree 
of  excitation,  and  in  some  eggs  the  isolation  from  the  parent  body 
is  sufhcient,  while  others  require  the  additional  stimulation  of 
extrusion  into  water,  and  for  still  others  the  further  change  result- 
ing from  entrance  of  the  sperm  is  necessary.  In  the  formation  of 
the  megaspore  and  microspore  in  plants  and  in  the  spermatogenesis 
of  animals  the  period  of  growth  between  other  divisions  and  matura- 
tion is  slight  or  practically  absent,  and  with  rare  exceptions  the  cells 
divide  equally  in  the  maturation  divisions.  Whether  in  these  cases 
also  the  maturation  divisions  are  initiated  by  a  stimulation  of  the 
cells  from  without  is  not  known,  but  the  probabihty  suggests  itself 
that  they  occur  as  the  result  of  a  physiological  or  physical  isolation 
of  the  cells. 

From  this  point  of  view  the  maturation  divisions  appear  to  be 
divisions  occurring  in  relatively  old  differentiated  cells  as  a  reaction 
to  physiological  or  physical  isolation  from  the  parent  body,  or  to 
this  factor  in  combination  with  others.  Their  peculiar  features 
are  apparently  associated  with  the  low  metabohc  rate  in  the  cells 
concerned.  In  the  mosses  and  ferns  the  spores  resulting  from  the 
maturation  divisions  undergo  rejuvenescence  and  begin  a  new 
developmental  and  vegetative  cycle  without  fertihzation,  but  in 
the  seed  plants  the  degree  of  rejuvenescence  is  apparently  slight 
in  most  cases  and  the  divisions  few  in  number,  and  in  animals, 
except  in  the  case  of  parthenogenic  eggs,  rejuvenescence  occurs 
only  after  fertilization. 

CONCLUSION 

In  the  present  chapter  the  attempt  has  been  made  to  show  that 
the  developmental  history  of  the  gametes  affords  no  adequate 
grounds  for  the  behef  that  germ  plasm  is  something  independent 
of  the  rest  of  the  organism.  There  is  no  proof  of  the  "segregation 
of  the  germ  plasm"  as  an  independent  entity  in  embryonic  develop- 
ment, but  the  germ  cells  are  very  evidently  determined  hke  other 


THE  GAMETES  IN  PLANTS  AND  ANIMALS  357 

parts  of  the  body  by  correlative  factors.  Moreover,  the  course  of 
development  of  the  gametes  bears  every  indication  of  being  a  pro- 
gressive differentiation  and  senescence,  not  fundamentally  dilTerent 
from  that  of  other  organs  of  the  body,  and  the  fully  developed 
gametes  are  physiologically  old,  highly  differentiated  cells,  which 
are  rapidly  approaching  death  and  in  most  cases  actually  do  die 
soon  after  maturity  unless  fertilization  occurs.  Whatever  their 
significance  for  inheritance  may  prove  to  be,  the  peculiar  features 
of  the  maturation  divisions  are  apparently  associated  with  the 
condition  of  advanced  physiological  age  and  low  metabolic  rate 
in  the  cells  where  they  occur.  These  cells,  whether  they  are 
the  spore  mother  cells  of  plants  or  the  gamete  mother  cells  of 
animals,  are  advanced  stages  of  a  period  of  progressive  develop- 
ment and  must  undergo  dedifferentiation  and  rejuvenescence 
before  they  can  enter  upon  a  new  period  of  development.  In  the 
plants  this  may  occur  to  a  greater  or  less  extent  without  fertiliza- 
tion in  the  development  of  the  gametophyte,  but  in  the  gametes  of 
animals,  with  the  exception  of  parthenogenic  eggs,  dedifferentia- 
tion and  rejuvenescence  occur  only  after  fertilization. 

REFERENCES 

AMilA,  K. 

191 1.  "  tjber  die  Differenzierung  der  Keimbahnzellen  bei  den  Kopepoden," 
Arch.f.  Zellforsch.,  VI. 

Ballowitz,  E. 

1886-1908.  The  following  is  a  partial  list  of  this  author's  papers  on  the 
structure  of  spermatozoa:  "Zur  Lehre  von  der  Struktur  der 
Spermatozoen,"  Anat.  Anz.,  I,  1886;  "Untersuchungen  iiber  die 
Struktur  der  Spermatozoen,"  Arch.f.  mikr.  Anal.,  XXXII,  188S; 
"Fibrillare  Struktur  und  Contractilitat,"  Arch.f.  d.  ges.  Physiol., 
XLVI,  1890;  "Untersuchungen  uber  die  Struktur  der  Sperma- 
tozoen," Arch.f.  mikr.  Anal.,  XXXVI,  1S90;  "Das  Rctzius'sche 
Endstiick  des  Siiugetierspermatozoen,"  Internal.  Monalsschr.  /, 
Anal.  u.  Physiol.,  VII,  1890;  "Untersuchungen  iiber  die  Struktur 
der  Spermatozoen.  Die  Spermatozoen  der  Insekten,"  Zeitschr. 
f.  wiss.  ZooL,  L,  1890;  "Die  Bedeutung  der  \'alentinschen 
Querbander  am  Spermatozoenkopf  der  Saugctiere,"  Arch.  f.  .inat. 
u.  Physiol.,  Anat.  Abt.,  1S91;  "Wcitere  Bcobachtungen  iiber  den 
feineren  Bau  der  Siiugetierspermatozoen,"  Zcilschr.  f.  wiss.  ZooL, 
LII,  1891 ;  "  Die  innere  Zusammensetzung  des  Spcrmatozoenkopfes 


358  SENESCENCE  AND  REJUVENESCENCE 

der  Saugetiere,"  Centralhl.  f.  Physiol.,  V,  1891;  "Weitere  sperma- 
tologische  Beitrage,"  Internat.  Monatsschr.  f.  Anal.  u.  Physiol., 
XI,  1894;  "tjber  die  Spermien  des  Flussneunauges  {Petromyzon 
fluvialilis  L.)  und  ihre  merkwiirdige  Kopfborste,"  Arch.  f.  mikr. 
Anal.,  LXV,  1904;  "Die  Spermien  des  Batrachiers  Pelodytes 
punctatus  Bonap.,"  Anat.  Anz.,  XXVII,  1905;  "Uber  einige 
Strukturen  der  Spermie  des  Spelcrpes  Juscus  Bonap.,"  Anat.  Anz. 
XXVIII,  1906;  "Zur  Kenntnis  der  Spermien  der  Cetaceen," 
Arch.  f.  mikr.  Anat.,  LXX,  1907;  "Uber  den  feineren  Bau  der 
eigenartigen  aus  drei  freien,  dimorphen  Fasern  bestehenden 
Spermien  der  Turbellarien,"  Arch.  f.  mikr.  Anat.,  LXX,  1907; 
"Die  kopflosen  Spermien  der  Cirripedien  {Balanus),"  Zeitschr.  f. 
wiss.  Zool.,  XCI,  1908. 

Ballowitz,  K. 

1894.  "Zur  Kenntnis  der  Samenkorper  der  Arthropoden,"  Internat. 
Motmtsschr.  f.  Anat.  u.  Physiol.,  XL 

Bancroft,  F.  W. 

1899.  "Ovogenesis  in  Distaplia  occidentalis  Ritter  (MS)  with  Remarks 
on  Other  Species,"  Bull,  of  the  Mus.  of  Comp.  Zool.  Harvard, 
XXXV. 

Beard,  J. 

1902.  "The  Germ  Cells:  Part  I,  Raja  batis,"  Zool.  Jahrhilcher;  Abt. 
f.  Anat.  u.  Ont.,  XVI. 

Belajeff,  W. 

1894.  "iJber  Bau  und  Entwickelung  der  Spermatozoiden  der  Pflanzen," 
Flora,  LXXIX. 

BOHMIG,  L. 

1890.  " Untersuchungen  iiber  rhabdocolen  Turbellarien:  II,  Plagio- 
stomina  und  Cylindrostomina  Graff,"  Zeitschr.  f.  wiss.  Zool.,  LI. 

BOSENBERG,  H. 

1905.  "Beitrage  zur  Kenntnis  der  Spermatogenese  bei  den  Arachnoiden, 
Zool.  Jahrbilcher;  Abt.  f.  Anat.  u.  Ont.,  XXI. 

BONNEVIE,  KrISTINE. 

1908.  "  Chromosomenstudien :  II,  Heterotypische  Mitose  als  Reifungs- 
charakter,  Arch.  f.  Zellforsch.,  II. 

BOVERI,  T. 

1887.  "Uber  Differenzierung  der  Zellkerne  wahrend  der  Furchung  des 
Eies  von  Ascaris  megalocephala,"  Anat.  Anz.,  11. 

1899.  "Die  Entwickelung  von  Ascaris  megalocephala  mit  besonderer 
Riicksicht  auf  die  Kernverhaltnisse,"  Festschrift  f.  von  Kupfer. 
Jena. 


THE  GAMETES  IX  PLANTS  ANT)  ANTMALS  359 

BOVERI,  T. 

1904.     Ergebnissc  ilbcr  die  Konslilution  der  chromatischen  Substanz  des 

Zcllkcrnes.     Jena. 
1910.     "Die  Potenzen  der  /l^car/^-Blaslomercn  bei  abgeandcrler  Fur- 
chung,"  Festschrift  zum  60.  Geburtstag  R.  llcrtwigs,  III. 
Braem,  F. 

1897.  "Die  geschlechiliche  Entwickelung  von  Plumaklla  fungosa," 
Zoologica,  X. 

Brefeld,  O. 

1872.     Botanische  Untersuchungen  ilber  Schimmclpilzc.     Heft  I. 

BUCHXER,  p. 

1910.  "Die  Schicksale  des  Kernplasmas  der  Sagitten  in  Reifung,  Befruch- 
tung,  Ovogenese  und  Spermatogenese,"  Fc5/5c7/r/y/  zum  60.  Geburt- 
stag R.  Hertwigs,  I. 

BURIAN,  R. 

1904.  "Chemie  der  Spermatozoen,  I,"  Ergebn.  d.  Physiol.,  III. 
1906.     "Chemie  der  Spermatozoen,  II,"  Ergebn.  d.  Physiol.,  X. 

Child,  C.  M. 

191 1.  "A  Study  of  Senescence  and  Rejuvenescence  Based  on  E.vperiments 
with  Planarians,"  Arch.  f.  Entwickclungsmcch.,  XXXI. 

CONKLIN,  E.  G. 

191 2.  "Cell  Size  and  Nuclear  Size,"  Jour,  of  Exp.  Zool.,  XII. 

1913.  "The  Size  of  Organisms  and  of  Their  Constituent  Parts  in  Rela- 
tion to  Longevity,  Senescence  and  Rejuvenescence,"  Pop.  Sci. 

Monthly,  August. 

Coulter,  J.  'M.,  B.^rxes,  C.  R.,  and  Cowles,  H.  C. 
1910.     A  Textbook  of  Botany.     New  York. 

Coulter,  J.  ]\I.,  and  Laxd,  W.  J.  G. 

1905.  "Gametophytes  and  Embr>'0  of  Torreya  laxifolia,"  Bot.  Gazette, 
XXXIX. 

Cunningham,  J.  T. 

1898.  "On  the  Histology  of  the  Ovary  and  of  the  Ovarian  Ova  in  Cer- 
tain Marine  Fishes,"  Quart.  Jour,  of  Micr.  Sci.,  XL. 

Downing,  E.  R. 

1909.  "The  Ovogenesis  of  Hydra,"  Zool.  Jahrbiichcr;  Abt.  f.  .\nat.  u. 
Ont.,  XXVHI. 

ElGENMANN,  C. 

1892.     "On  the  Precocious  Segregation  of  the  Sex  Cells  of  Micronutrus 

aggregatus,''  Jour,  of  Morphol.,  V. 
1896a.  "Sex   Differentiation   in   the   \'iviparous  Teleost  Cymatogaster" 

Arch.f.  Entwickelungsmech.,  IV. 


360  SENESCENCE  AND  REJUVENESCENCE 

ElGENMANN,  C. 

18966.  "The  Bearing  of  the  Origin  and  Differentiation  of  the  Sex-Cells 
of  Cymatogaster  on  the  Idea  of  the  Continuity  of  the  Germ  Plasm," 
Am.  Nat.,  XXX. 

Farmer,  J.  B.,  Moore,  J.  E.  S.,  and  Walker,  C.  E. 

1904.  "tjber  die  Ahnlichkeit  zwischen  den  Zellen  maligner  Neubil- 
dungen  beim  jNIenschen  und  denen  normaler  Fortpflanzungs- 
gewebe, "  Biol.  CentralU.,  XXIV. 

Felix,  W.,  and  Buhler,  A. 

1906.  "Die  Entwickelung  der  Keimdriisen  und  Ausfiihrungsgange,"  0. 
Her  twigs  Handhuch  der  vergleichenden  Entwickltmgslehre,  Bd.  Ill, 
T.  I.    Jena. 

Galton,  F. 

1872.     "On  Blood-Relationship,"  Proc.  Roy.  Soc,  XX. 

Hacker,  V. 

1897.     "Die  Keimbahn  von  Cyclops,"  Arch.  f.  niikr.  Anat.,  XLIX. 
1900.     "Mitosen  im  Gefolge  amitosenahnlicher  Vorgange,"  Anat.  Anz., 

XVII. 
1902.     "tJber  das  Schicksal  der  elterlichen  und  grosselterlichen  Kern- 

anteile,"  Jen.  Zeitschr.f.  Naturwiss.,  XXX. 
1904.     "liber  die  in  malignen  Neubildungen  auftretenden  heterotypischen 

Teilungsbilder,"  Biol.  CentralU.,  XXIV. 

1907.  "Die  Chromosomen  als  angenommene  Vererbungstrager,"  Ergehn. 
u.  Fortschr.  d.  ZooL,  I. 

1912a.  Kapitel  "Zeugungslehre"  in  A.  Langs  Handhuch  d.  Morphol.  d. 

wirbellosen  Tiere,  Bd.  II.     Jena. 
191 26.  Allgemeine  Vererhiingslehre,  II.  Auflage.     Braunschweig. 

Hasper,  M. 

191 1.  "Zur  Entwicklung  der  Geschlechtsorgane  von  Chironomus,"  ZooL 
Jahrhilcher;  Abt.f.  Anat.  u.  Ont.,  XXXI. 

Hegner,  R.  W. 

1909.  "The  Origin  and  Early  History  of  the  Germ  Cells  in  Some  Chrys- 
omelid  Beetles,"  Jour,  of  Morphol.,  XX. 

191 1.  "Experiments  with  Chrysomelid  Beetles:  III,  The  Effects  of 
Killing  Parts  of  the  Eggs  of  Leptinotarsa  decetnlineata,"  Biol. 
Bull.,  XX. 

191 2.  "The  History  of  the  Germ  Cells  in  the  Paedogenetic  Larvae  of 
Miaslor,"  Science,  XXXVI. 

1914a.  "Studies  on  Germ  Cells:  I,  The  History  of  the  Germ  Cells  in 
Insects  with  Special  Reference  to  the  isTci/M^a/m -Determinants;  II, 
The  Origin  and  Significance  of  the  Keimbahn-D etevminants  in 
Animals,"  Jour,  of  Morphol.,  XXV. 


THE  GAMETES  L\  PLANTS  AMJ  ANIMALS  361 

Hegxer,  R.  W. 

1914&.  "Studies   on    Germ    Cells:     III,   The   Origin  of   the   Kcimbahn- 

Determinants  in  a  Parasitic  Hymenopleron,  Copidosonui,"  Atutl. 

Anz.,  XLVL 
1914c.   The  Germ-Cell  Cycle  in  Animals.    New  York. 

Jager,  G. 

1877.     " Physiologische  Briefe,"  Kosmos,  I. 

Kahle,  W. 

1908.     "Die  Paedogenese  der  Cecidomyiden,"  Zoologica,  XXI. 

Klein,  L. 

1889.     "Morphologische    und    biologische    Studien    iiber    die    Gattung 
Volvox,"  Jahrhiicher  f.  wiss.  Bot.,  XX. 

KOLTZOFF,  N.  K. 

1906a.  "Studien  iiber  die  Gestalt  der  Zelle:    I,  Untersuchungen  iiber 

die  Spcrmien  der  Decapodcn,"  Arch.  f.  mikr.  An^it.,  LX\TI. 
19066.  "Uber  das  Skelett   des  lierischen  Spermiums,"   Biol.  Centralbl., 

XXVL 

1908.  "Studien  ubcr  die  Gestalt  der  Zelle:    II,  Untersuchungen  uber 
das  Kopfskelett  des  tierischen  Spermiums,  Arch.  J.  Zclljorsch.,  II. 

KORSCHELT,  E. 

1891.     "Beitrage  zur  Morphologic  und  Physiologie  des  Zellkernes,"  Zool. 
Jahrbiicher;  Abt.f.  Anat.  u.  Out.,  IV. 

KoRSCHELT,  E.,  and  Heider,  K. 

1902.     Lchrbuch  der  verglcichoidcn  Entwicklungsgeschichte  der  wirbclloscn 
Tiere.     AUgem.  Teil,  I.  Lieferung.     Jena. 

LiLLIE,  F.  R. 

1912.     "Studies  of  Fertilization  in  Nereis:   III,  The  :Morpholog>'  of  the 
Normal  Fertilization  of  Nereis,"  Jour,  of  Exp.  Zool.,  XII. 

Luther,  A. 

1904.     "Die  Eumesostominen,"  Zeitschr.  f.  iviss.  Zool..  LXXMl. 

Maige,  M. 

1909.  "Recherches  sur  la  respiration  de  I'etamine  et  du  pistil,"  Rr^'.  gin. 

de  bot.,  XXI. 
191 1.     "Recherches   sur   la   respiration    des  ditKrenles  pieces  lloralcs." 
Ann.  des  sci.  nal.;  Bot.,  (9).  XIV. 

Marchal,  El.,  et  Marcilal,  Em. 

1907.     "Aposporie  et  se.xualite  chcz  les  mousses.     I,"  Bull.  .lead.  Roy.  de 

Belgiquc;   CI.  des  Sci. 
1909.     "Aposporie,"  etc.    U,  Bull.  Acad.  Roy.  de  Bclgiijue;   CI.  des  Sci. 
191 1.     "Aposporie,"  etc.    Ill,  Bull.  Acad.  Roy.  dc  Belgiquc;  CI.  des  Sci. 


362  SENESCENCE  AND  REJUVENESCENCE 

Marchal,  Em. 

191 2.     "Recherches  cytologiques  sur  le  genre  Atnblystegiim,"  Bull.  Acad. 
Roy.  de  Belgique;  CI.  des  Sci. 

Mathews,  A.  P. 

1897.     "Zur   Chemie   der   Spermatozoen,"   Zeitschr.  f.   physiol.   Chem., 
XXIII. 

Merrell,  W.  D. 

1900.  "A  Contribution  to  the  Life  History  of  Silphium,"  BoL  Gazette, 
XXIX. 

Meves,  F. 

1899.  "iJber  Struktur  und  Histogenese  der  Samenfaden  des  Meerschwein- 
chens,"  Arch.  f.  mikr.  Anat.,  LTV. 

1903.  "iJber  oligopyrene  und  apyrene  Spermien  und  iiber  ihre  Entste- 
hung,  nach  Beobachtungen  an  Paludina  und  Pygaera'^  Arch, 
f.  mikr.  Anat.,  LXI. 

MiNOT,  C.  S. 

1908.  The  Problem  of  Age,  Growth  and  Death.     New  York. 
Nawaschin,  S.  ^ 

1900.  "iiber  die  Befruchtungsvorgange  bei  emigen  Dicotyledoneen," 
Berichte  d.  deutsch.  hot.  Gesell.,  XVIII. 

NUSSBAUM,  M. 

1880.  "Zur  Differenzierung  des  Geschlechts  im  Tierreich,"  Arch.  f. 
mikr.  Anat.,  XVIII. 

SCHEBEN,  L. 

1905.  "Beitrage  zur  Kenntnis  des  Spermatozoons  von  Ascaris  tnegalo- 
cephala,"  Zeitschr.  f.  wiss.  Zool.,  LXXIX. 

Schiller,  J. 

1909.  "liber  kiinstliche  Erzeugung  "primitiver"  Kemteilungsfiguren  bei 
Cyclops,"  Arch.  f.  Entwickelungsmech.,  XXVII. 

SCHUBMANN,  W. 

1905.     "iiber  die  Eibildung  und  Embryonalentwicklung  von  Fasciola 
hepatica  L.,"  Zool.  Jahrbilcher;   Abt.f.  Anat.  u.  Ont.,  XXI. 
Sharp,  L.  W. 

1912.  "Spermatogenesis  in  Equisetum,"  Bot.  Gazette,  LIV. 
Steudel,  H. 

1911a.   "Zur    Histochemie    der    Spermatozoen."    I.    Mitt.     Zeitschr.   /. 

physiol.  Chem.,  LXXII. 
191 16.   "Zur  Histochemie,"  etc.     II.  Mitt.      Zeitschr.  f.  physiol.  Chem., 

LXXIII. 

1913.  "Zur  Histochemie,"  etc.  III.  Mitt.  Zeitschr.  f.  physiol.  Chem., 
LXXXIII. 


THE  GAMETES  IN  PLANTS  AND  ANIMALS  363 

zuR  Strassen,  O. 

1896.     "Embr>'onalentwicklung    der    Ascaris    mcgaloccp/tala,"    Arch.  f. 
Entivickclungsmcch.,  111. 

Tannreuther,  G.  W. 

1907.  "History  of  the  Germ  Cells  and  Early  EmbryoloRy  of  Certain 
Aphids,"  Zool.  JahrhUchcr;  Abt.J.  Anal.  u.  Onl.,  XXIW 

Waldeyer,  W. 

1906.     "Die  Geschlechtszellen,"  0.  Hertwigs  Hatidbiich  der  verglekhaiden 
Entwickelungskhre,  Bd.  I,  T.  L    Jena. 
Webber  H.  J. 

1901.     "Spermatogenesis   and   Fecundation  of  Zamia,"    U.S.   Dcpt.   of 
Agric,  Bureau  of  Plant  Industry,  Bull.  No.  2. 
Weismann,  a. 

1877.     "Beitrage   zur   Naturgeschichte   der   Daphnoiden,"    T.    \\.    Ill 

und  IV,  Zeitschr.f.  wiss.  Zool.,  XXVIII. 
1885.     Die  Continuitdt  dcs  Kcimplasmas  als  Grundlage  ciner  Theorie  der 

Vererbung.     Jena. 
1892.     Das  Keimplasma.     Jena. 

Wheeler,  W.  M. 

1900.     "The  Development  of  the  Urogenital  Organs  of  the  Lamprey," 
Zool.  Jahrbiicher;  Abt.  f.  Anat.  u.  Out.,  XIII. 

Winkler,  H. 

1908.  "tJber  Parthenogenesis  und  Apogamie  im  Pflanzenreiche,"  Pro- 

gressus  rei  bat.,  II. 

Yamanouchi,  S. 

1908.     "Spermatogenesis,  Oogenesis  and  Fertilization  in  Ncpltrodium," 
Bat.  Gazette,  XLV, 

Zacharl\s,  O. 

1913.     "Die  Chromatin-Diminution  in  den  Furchungszellen  von  Ascaris 
megalocephala,"  Anat.  Anz.,  XLIII. 

ZojA,  R. 

1896.     "Untersuchungen    iiber    die    Entwicklung    der    Ascaris    megalo- 
cephala," Arch.  f.  mikr.  Anat.,  XL VII. 


CHAPTER  XIV 
CONDITIONS  OF  GAMETE  FORMATION  IN  PLANTS  AND  ANIMALS 

In  all  organisms  the  production  of  the  gametes  or  sexual  cells, 
the  condition  known  in  the  higher  forms  as  sexual  maturity,  is 
apparently  associated  with  certain  other  physiological  conditions 
which,  at  least  in  the  higher  animals,  are  characteristic  of  relatively 
advanced  stages  of  development.  The  present  chapter  is  an 
attempt  to  estabhsh  a  general  foundation  for  the  interpretation  of 
the  various  data  of  observation  and  experiment.  This  foundation 
is  in  brief  the  view  that  the  production  of  gametes  is  simply  one 
feature  of  the  orderly  development  of  the  organism  and  is  therefore 
associated  with  certain  conditions  in  other  organs  and  is  related 
to  processes  of  differentiation  and  senescence  in  the  organism  as  a 
whole. 

CONDITIONS    OF    GAMETE    FORMATION   IN  THE   ALGAE    AND   FUNGI 

It  was  formerly  beheved  that  the  essential  factors  determining 
reproduction,  and  particularly  gametic  or  sexual  reproduction  in 
plants  were  internal,  and  that  external  factors  had  but  little  to  do 
with  the  process.  But  various  investigators,  and  particularly 
Klebs,  have  demonstrated  that  the  sequence  of  events  in  the  hfe 
cycle  of  plants  can,  to  a  very  large  extent,  be  controlled  by  external 
factors.  Klebs's  work  along  this  line  has  been  discussed  in  chap,  x 
in  connection  with  agamic  reproduction  (pp.  249-52),  and  here  only 
certain  points  which  concern  the  formation  of  gametes  need  be 
considered.  Klebs  mentions  the  fact  that  where  spore  formation 
or  gamete  formation  or  both  occur  in  cultures  of  Vaucheria  and 
Saprolegnia,  in  addition  to  what  he  calls  growth,  which  is  what  I 
have  called  vegetative  reproduction,  these  more  specialized  repro- 
ductive processes  occur  on  the  older  parts  of  the  plant  body  and 
the  vegetative  on  the  younger.  He  also  concludes  that  the  attain- 
ment of  a  certain  concentration  of  the  organic  substances  in  the 
plant  is  an  essential  condition  for  such  reproductive  processes  and 
that  for  gametic  reproduction  the  concentration  must  be  higher 

364 


CONDITIONS  OF  GAMETE  EORMATKjN  365 

than  for  spore  formation.  According  to  Klebs.  these  difTerences 
in  concentration  concern  primarily  the  nutritive  substances,  but 
it  seems  probable  that  the  protoplasm  of  the  cells  may  also  be 
involved.  I  have  endeavored  to  show  that  vegetative  reproduction, 
in  consequence  of  the  regressive  changes  associated  with  it,  retards 
or  inhibits  the  progress  of  senescence  (pp.  237-55).  The  conditions 
which  bring  about  the  formation  of  gametes  in  Klebs's  experiments 
decrease  or  check  vegetative  growth,  and  the  cells  of  the  plant 
accumulate  organic  substance  and  so  attain  a  condition  of  greater 
physiological  age  with  a  lower  rate  of  metabohsm  than  during  active 
vegetative  reproduction.  Apparently  spore  formation  occurs  at  an 
earher,  and  gamete  formation  at  a  later,  stage  of  this  process  of 
senescence. 

In  the  algae  and  fungi,  with  their  low  degree  of  individuation, 
certain  parts  of  the  plant  may  under  certain  conditions  become  old 
while  others  remain  young,  and  in  such  cases  gamete  formation 
and  vegetative  reproduction  may  occur  simultaneously,  the  one  in 
the  older,  the  other  in  the  younger,  parts.  The  results  of  Klebs's 
experiments  do  not  then  indicate  that  the  plant  has  no  definite  life 
history,  but  merely  that  because  of  its  capacity  for  vegetative 
reproduction  it  can  be  prevented  indefinitely  from  attaining  the 
later  stages.  But  when  it,  or  a  part  of  it,  attains  these  stages,  the 
more  specialized  reproductive  processes  appear,  and  the  formation 
of  gametes  is  apparently  characteristic  of  a  more  advanced  stage 
than  spore  formation.  Even  after  gamete  formation,  however, 
the  plant  does  not  necessarily  die,  but  under  the  proper  conditions 
may  resume  vegetative  reproduction  or  spore  formation.  In  thos.e 
cases  where  gametic  reproduction  may  be  induced  before  vegetative 
reproduction  has  continued  for  any  considerable  length  of  time  it  is 
probable  that  the  conditions  bring  about  premature  aging,  and  the 
plant  very  soon  attains  a  certain  physiological  state  which  under 
other  conditions  may  arise  only  after  a  long  time  or  not  at  all. 

The  process  of  aging  in  these  lower  plants  is  then  very  inti- 
mately associated  with  external  conditions.  Under  certain  con- 
ditions progressive  senescence  and  gamete  formation,  under  others 
a  balance  between  senescence  and  rejuvenescence,  with  continuous 
vegetative    reproduction,    may    occur.     A    life   cycle   exists   as   a 


366  SENESCE^XE  AND  REJUVENESCENCE 

possibility  for  the  lower  plant,  and  gamete  formation  is  a  feature 
of  its  later  stages,  but  since  physiological  progression  may  be 
experimentally  accelerated,  retarded,  or  inhibited  by  controlling  the 
relation  between  progression  and  regression,  the  life  cycle  does  not 
appear  as  a  definite,  uniform,  internally  determined  sequence  of 
events  such  as  occurs  in  the  higher  animals. 

CONDITIONS  OF  GAMETE  FORMATION  IN  MOSSES  AND  FERNS 

In  mosses  and  ferns  the  life  cycle  is  complicated  by  an  alternation 
of  sporophyte  and  gametophyte  generations,  each  of  which  possesses 
a  characteristic  different  structure.  The  gametophyte  produces 
sexual  organs  in  which  the  gametes  develop,  and  the  gametes  after 
fertihzation  give  rise  to  the  sporophyte  which  produces  asexual 
spores,  and  these  produce  another  gametophyte  generation.  In 
mosses  the  gametophyte  is  the  vegetative  generation,  and  the  sporo- 
phyte does  not  lead  an  independent  Hfe  but  develops  upon  the 
gametophyte.  In  the  ferns,  on  the  other  hand,  both  the  sporo- 
phyte, the  fern  plant,  and  the  gametophyte,  the  prothallium,  lead 
an  independent  vegetative  life. 

In  both  mosses  and  ferns  the  production  of  sexual  organs  and 
gametes  on  the  gametophyte  occurs  only  after  a  certain  period  of 
vegetative  activity  which  may  vary  in  length  with  external  con- 
ditions; in  other  words,  gamete  formation  seems  to  be  characteristic 
of  a  certain  physiological  condition  which  does  not  exist  in  the  early 
life  of  the  gametophyte  but  arises  only  later.  This  condition  evi- 
dently corresponds  to  the  condition  of  sexual  maturity  in  the  higher 
animals.  Moreover,  after  producing  sex  organs  and  gametes  the 
gametophyte  dies,  except  where  parts  of  it  produce  new  gameto- 
phytes  asexually. 

Vegetative  agamic  reproduction  in  the  gametophytes  occurs 
very  widely  and  in  a  great  variety  of  forms  among  both  mosses  and 
ferns  and  leads  directly  to  the  formation  of  new  gametophyte  indi- 
viduals. In  certain  species,  or  under  certain  external  conditions, 
vegetative  reproduction  of  the  gametophyte  may  continue  indefi- 
nitely, and  sex  organs  and  gametes  do  not  appear  or  appear  very 
rarely.  This  is  conspicuously  the  case  in  many  of  the  so-called 
true  mosses,  the  Bryales,  in  which  the  degree  of  individuation  in  the 
gametophyte  is  evidently  very  slight,  and  vegetative  reproduction 


COXDITIOXS  OF  GAMETE  FORMATION'  367 

occurs  by  the  isolation  of  leaves,  branches,  specialized  gemmae, 
etc.,  and  in  many  cases  from  single  cells  of  various  regions  of  the 
gametophy  te.  In  many  such  species  sex  organs  and  gametes  appear 
only  occasionally,  or  very  rarely,  and  vegetative  propagation  of  the 
gametophyte  may  continue  indefinitely. 

If  the  viewpoint  developed  in  preceding  chapters  has  any 
foundation  in  fact,  we  must  believe  that  in  every  one  of  these 
vegetative  reproductions  a  new  individuation  and  some  degree  of 
reconstitutional  change  in  the  cells  involved  occur.  And  again,  if 
this  is  the  case,  the  new  individuals  resulting  from  reproduction 
are,  at  least  to  a  shght  degree,  younger  physiologically  than  the 
individual  of  which  they  originally  formed  a  part.  The  result  of 
continued  vegetative  reproduction,  whether  it  is  induced  by  external 
factors  or  determined  by  a  low  degree  of  individuation  in  the 
species,  is  then  to  prevent  the  gametophyte  generation  from  attain- 
ing physiological  maturity;  consequently  the  specializations  and 
morphological  differentiations  characteristic  of  maturity,  viz..  the 
development  of  sex  organs  and  gametes,  do  not  take  place,  or  take 
place  only  rarely  when  individuals  in  consequence  of  external  or 
internal  conditions  happen  to  reach  maturity. 

Various  botanists  have  suggested  that  in  such  cases  the  vege- 
tative reproduction  is  the  consequence  of  the  failure  to  produce 
sex  organs  and  gametes,  but  the  facts  point  to  the  opposite  con- 
clusion— that  the  continued  vegetative  reproduction  with  the 
accompanying  reconstitution  simply  prevents  the  individual  from 
attaining  maturity.  Whether  in  any  case  the  capacity  for  gamete 
formation  has  been  lost  or  is  disappearing,  can  be  determined  only 
after  the  most  extensive  and  intensive  research.  But  the  low  degree 
of  individuation  accounts  without  difficulty  for  the  preponderance 
of  vegetative  reproduction,  and  there  is  no  reason  for  believing  that 
a  loss  in  the  capacity  for  gamete  formation  has  occurred.  Failure  to 
produce  gametes  in  such  cases  probably  means  only  that  the  indi- 
vidual never  attains  the  physiological  condition  of  which  that  par- 
ticular process  is  a  feature. 

The  occurrence  of  apogamy  in  the  ferns'  indicates,  as  already 
pointed  out  (p.  322).  that  there  is  no  segregation  of  germ  plasm 

'  Farlow,  '74;  de  Bary,  '78;  Hcim.  '96;  Farmer  and  Digby.  '07;  Woronin,  '08; 
Winkler,  'oS. 


368  SENESCENCE  AND  REJUVENESCENCE 

in  the  gametes  alone.  Apparently  the  sporophyte  may  arise  from 
any  vegetative  cell  of  the  gametophyte.  But  the  fact  that  apoga- 
mous  development  of  a  sporophyte  often  begins  as  a  transformation 
of  the  sex  organs  either  antheridia  or  archegonia,  or  is  correlated 
with  the  incomplete  development  or  degeneration  of  the  sex  organs 
or  of  the  eggs,  suggests  that  some  sort  and  some  degree  of  phys 
iological  correlation  exists  between  apogamy  and  formation  oi 
gametes.  It  seems  not  improbable  that  the  degree  of  individuation 
is  in  such  cases  not  quite  sufficient  to  carry  the  organism  through 
the  entire  cycle,  and  the  physiological  isolation  of  vegetative  cells 
in  the  stages  near  maturity  leads  to  reproduction  of  a  sporophyte, 
i.e.,  the  vegetative  cells  have  the  same  developmental  capacity  as 
the  egg,  but  are  less  specialized  and  so  do  not  require  fertilization. 
Up  to  the  present,  however,  other  aspects  of  the  process  of  apog- 
amy have  received  much  more  attention  than  its  physiology  and 
relation  to  the  individuation  of  the  organism  in  which  it  appears, 
and  any  attempt  at  physiological  interpretation  must  at  present 
be  a  mere  guess. 

CONDITIONS  OF  GAMETE  FORMATION  IN  THE  SEED  PLANTS 

In  the  mosses,  ferns,  and  related  forms  the  two  generations,  the 
asexual  sporophyte  and  the  gametophyte  w^hich  produces  sexual 
organs  and  gametes,  are  more  or  less  distinct  and  separate  organisms 
with  different  morphological  structure  and  different  habit.  In  the 
seed  plants,  however,  the  sporophyte  generation  has  become  by  far 
the  most  conspicuous  feature  of  the  Kfe  cycle,  and  the  gametophyte 
generation  is  reduced  to  the  pollen  grain  and  the  embryo  sac  of  the 
flower.  The  flower  is  commonly  defined  as  an  axis  or  shoot  of 
which  some  parts  bear  sexual  organs.  The  flower,  like  the  vegeta- 
tive shoots,  arises  from  an  agamic  bud,  but  this  bud  is  evidently 
more  highly  specialized  than  the  vegetative  buds,  for  its  parts  are 
variously  modified  and  differentiated  in  various  directions  into  the 
parts  of  the  flower.  INIoreover,  the  axis  which  produces  the  flower 
usually  does  not  continue  to  grow  for  a  long  time,  or  indefinitely, 
but  the  growth  is  narrowly  limited  and  the  development  of  the 
flower  ends  under  the  usual  conditions  in  death.  Evidently  the 
flower  represents  the  most  advanced  or  the  highest  stage  in  the 


CONDITIONS  OF  GAMETE  FORMATION  369 

differentiation  of  the  plant  body.  lioth  moqihologically  and 
physiologically  it  is  a  much  more  highly  differentiated  and  special- 
ized system  than  the  vegetative  axes  of  the  plant. 

This  being  the  case,  we  should  expect  to  find  the  llower  as  the 
final  stage  of  development,  as  the  expression  of  maturity  of  the 
plant.  Among  the  flowering  plants  this  appears  in  general  to  be 
the  case.  The  young  plant  grows,  produces  new  vegetative  axes, 
and  in  most  cases  becomes  what  the  zoologist  would  term  an  asexual 
colony,  but  after  a  longer  or  shorter  period  of  such  vegetative  growth 
and  reproduction,  varying  in  different  plants  from  a  few  weeks  to 
many  years,  flower  buds  appear  in  place  of  certain  or  all  of  the 
vegetative  buds,  gametes  are  produced,  and  seeds  are  formed. 
In  many  plants  vegetative  growth  ceases  when  flowering  occurs, 
and  flowering  is  followed  by  death  of  the  whole  plant,  except  the 
seeds,  but  in  others  the  sequence  may  be  repeated  an  indc^finite 
number  of  times  during  the  life  of  the  plant. 

To  all  appearances  then  these  plants  have  a  definite  life  history, 
vegetative  growth  and  reproduction  of  vegetative  axes  being 
characteristic  of  the  earlier  stages  and  the  development  of  flowers 
and  gametic  reproduction  of  the  later  stages.  In  those  plants 
where  the  sequence  is  repeated  periodically,  different  shoots  or  axes, 
that  is,  different  plant  individuals,  are  concerned  in  each  pericd. 
Moreover,  it  is  a  well-known  fact  that  in  general  cuttings  from 
plants  in  bloom  or  ready  to  bloom  are  likely  to  bloom  earlier  than 
cuttings  from  plants  which  are  still  in  the  stage  of  active  vege- 
tative growth.  Such  facts  indicate  clearly  that  flowering  is  an 
expression  of  intarnal  conditions  which  are  characteristic  of  a  rela- 
tively advanced  stage  in  the  hfe  of  the  plant  or  in  a  seasonal  or 
other  period  of  metabolic  activity  and  growth. 

But  certain  facts  of  observation  and  experiment  have  often  been 
regarded  as  pointing  to  a  somewhat  different  conclusion.  Fir.st 
among  these  is  the  familiar  fact,  to  which  attention  has  already  been 
called  (pp.  239-44),  that  many  plants  live  and  grow  incL-finilely 
without  sexual  reproduction.  This  is  true,  nt)t  only  of  many 
rhizome  plants,  in  which  the  rhizome  or  rootstock  grows  con- 
tinuously and  produces  new  buds  and  roots,  and  from  lime  to 
time  branches,  while  at  the  other  end  death  continually  advances, 


370  SENESCENCE  AND  REJUVENESCENCE 

but  it  apparently  holds  for  at  least  many  other  plants  as 
well.  Propagation  by  cuttings  may  be  continued  for  a  large 
number  of  generations  and  probably  indefinitely  in  many 
plants,  and  some  plants  are  not  known  to  reproduce  sexually  in 
nature. 

IMany  of  our  cultivated  plants  have  been  bred  agamically, 
either  wholly  or  to  a  large  extent,  for  a  long  period  of  years.  The 
banana  is  one  of  the  most  conspicuous  examples,  the  sugar  cane 
another,  and  in  various  species  of  willow  and  poplar  and  many 
plants  grown  from  bulbs  or  tubers,  e.g.,  the  potato,  the  agamic 
method  of  propagation  is  the  usual  one. 

]\Iobius  ( '97)  has  brought  together  a  large  number  of  these  cases, 
and  has  c  onsidered  particularly  those  in  which  agamic  propagation 
for  a  longer  or  shorter  time  was  apparently  followed  by  the  deteriora- 
tion or  the  dying  out  of  the  stock.  In  many  cases  parasitic  diseases 
are  responsible  for  this  result,  in  other  cases  cUmatic  or  other  ex- 
ternal factors,  and  Mobius  concludes  that  there  are  no  grounds  for 
believing  that  agamic  propagation  necessarily  results  in  an  aging, 
deterioration,  and  death  of  the  stock. 

Mobius  has  also  discussed  the  facts  bearing  on  the  question 
whether  continued  agamic  propagation  may  lead  to  loss  of  the  power 
of  gametic  reproduction  and  concludes  that,  in  at  least  most  cases, 
gametic  reproduction  is  prevented  by  external  factors  and  agamic 
reproduction  takes  its  place.  It  is  an  undoubted  fact  that  plants 
which  do  not  reproduce  sexually  usually  show  a  high  degree  of 
agamic  reproductive  capacity  of  one  form  or  another.  While  it  is 
not  possible  at  present  to  analyze  most  of  these  cases,  they  all  fall 
readily  into  hne  with  the  view  that  gametic  reproduction  is  char- 
acteristic of  a  certain  relatively  advanced  stage  of  the  life  history 
of  the  individual,  and  that  the  individual  cannot  attain  this  stage 
under  conditions  which  bring  about  a  continued  or  periodic  breaking 
up,  physiologically  speaking,  into  new  individuals.  If  conditions 
in  nature  or  under  cultivation  favor  continued  vegetative  growth, 
new  individuations  continually  occur  and  the  reconstitutional 
changes  connected  with  this  continued  agamic  reproduction  prevent 
any  individual  from  attaining  the  condition  of  maturity.  Or  the 
conditions  may  decrease  the  degree  of  individuation  of  the  species 


CONDITIONS  OF  GAMETE  FORMATION 


.5/ 


so 


by  altering  the  rate  of  metabolism,  or  in  some  other  way.  and 
lead  to  vegetative  or  other  forms  of  agamic  reproduction.' 

From  this  point  of  view,  the  absence  or  rare  occurrence  of 
gametic  reproduction  in  various  plants,  either  in  nature  or  under 
cultivation,  is  not  in  any  sense  the  factor  which  determines  increased 
agamic  reproduction,  but  the  agamic  reproduction  prevents  the 
organism  from  attaining  the  physiological  condition  in  which 
gametic  reproduction  occurs.  Teleological  interpretation  of  such 
cases  is  entirely  unnecessary  and  beside  the  point.  Whether  one 
form  of  reproduction  or  another  occurs  depends  upon  the  physi- 
ological condition  of  the  individual.  In  the  physiologically 
young,  immature  individual,  whether  it  be  a  unicellular  plant,  a 
single  plant  axis,  or  a  whole  multiaxial  plant,  reproduction,  when  it 
occurs,  is  agamic,  while  the  formation  of  gametes  occurs  in  the  older, 
mature  individual. 

This  conclusion  may  seem  at  first  glance  to  conflict  seriously  with 
certain  other  observational  and  experimental  data  concerning  the 
occurrence  and  experimental  production  of  flowers.  Flowers  appear 
frequently,  either  as  an  anomaly  in  nature  or  under  experimental 
conditions,  on  plants  which,  as  regards  length  of  time  from  the  seed, 
as  well  as  size  and  morphological  condition,  are  in  an  early  stage 
of  development  and  young.  The  experimental  investigations  of 
Vochting,  Klebs,  and  others  have  demonstrated  that  the  occurrence 
of  flowering  may  be  controlled  within  wide  limits  by  means  of 
various  external  conditions.' 

Vochting's  experiments  on  Mimulus  tilingii  show  ver>'  clearh* 
the  significance  of  fight  for  flowering.  In  a  certain  low  illumination 
in  which  vegetative  growth  is  possible  the  inflorescence  begins  to 
develop,  but  the  preformed  flower  buds  cease  their  development  at 

'  The  following  references  will  serve  as  a  guide  to  the  literature  of  the  subject. 
Mobius  ('97)  presents  and  describes  numerous  facts,  largely  observational  rather 
than  experimental,  bearing  upon  the  problem.  Diels  ('06)  has  brought  together  many 
cases  of  premature  flowering  or  "nanism,"  both  from  his  own  observations  and  from 
the  literature.  The  experimental  investigations  of  Vochting  ('93),  Klebs  ('03,  '04, 
'06),  and  others  demonstrate  that  the  occurrence  of  flowering  may  be  controlled  within 
wide  limits  by  means  of  external  fattors.  Jost  ('oS,  pp.  439-40)  gives  a  goo<l  gcner.il 
survey  of  the  subject.  Additional  references  are  Benecke, '06;  Doposchcg-Uhldr.  'u; 
A.  Fischer,  '05;  Goebel,  '08,  pp.  6,  10,  117,  190;  Loew,  '05.  These  papers  contain 
further  references. 


372  SENESCENCE  AND  REJUVENESCENCE 

an  early  stage,  and  instead  of  flowers  axillary  buds  become  active 
and  grow  out  into  vegetative  branches  and  the  inflorescence  is 
transformed  into  a  vegetative  complex  and  the  formation  of  gametes 
does  not  occur.  It  should  be  noted  that  in  this  case  it  is  only  the 
later  stages  of  flower  development  which  are  inhibited  by  the  low 
light  intensity.  The  specialization  or  change,  of  whatever  character 
it  may  be,  which  determines  the  development  of  an  inflorescence 
has  occurred  in  these  plants,  but  it  stops  at  a  certain  stage  and  with 
its  cessation  new  vegetative  individuals  arise  in  consequence  of 
physiological  isolation,  and  the  vegetative  life  is  resumed. 

Klebs  records  similar  results  for  various  species  and  states  that 
in  all  plants  which  do  not  possess  a  considerable  volume  of  reserves 
a  decrease  in  illumination  suppresses  the  formation  of  flowers. 
According  to  Klebs,  this  influence  of  iUumination  on  flowering  is 
essentially  a  matter  of  photosynthesis.  Blue  Hght,  which  decreases 
photosynthesis,  acts  hke  decreased  illumination  on  flowering,  while 
in  red  Hght,  by  which  photosynthesis  is  less  affected,  flowering 
occurs. 

Various  other  conditions — temperature,  water,  nutritive  salts, 
etc. — have  been  found  to  influence  the  occurrence  of  flowering.  In 
summing  up  his  experiments  on  flowering  plants  in  general  Klebs 
says: 

For  the  formation  of  flowers  the  relations  between  the  internal  physico- 
chemical  conditions  must  be  different  from  those  in  which  vegetative  growth 
occurs.  I  believe  that  a  quantitative  increase  in  concentration  of  the  organic 
substances,  with  all  its  physical  and  chemical  consequences,  plays  an  essential 
part  m  the  transition  from  growth  to  reproduction.  All  external  factors  may 
influence  the  occurrence  of  flowering  favorably  or  unfavorably,  according  to 
their  intensity,  their  interrelations  with  each  other,  and  the  specific  nature  of 
the  plant,  their  effect  depending  upon  the  relations  among  the  internal  con- 
ditions which  they  bring  about.' 

In  a  later  paper  Klebs  states  the  results  of  his  extensive  experi- 
ments on  Sempervivum  funkii  in  somewhat  more  definite  form.  He 
says: 

I  begin  with  a  vigorous,  previously  well-nourished  rosette  which  is  ready 
to  bloom  and  make  the  experiments  which  determine  its  fate  before  or  during 
^he  primordial  stages  of  flower  development.     The  results  are  as  follows: 

'  Klebs,  '04,  pp.  553-54- 


CONDITIONS  OF  G.UIETE  FOinrATIOX  373 

1.  In  bright  light  with  active  photosynthesis  and  intense  absorption  of 
water  and  salts  active  vegetative  growth  results. 

2.  In  bright  light  with  active  photosynthesis  but  with  limited  absorption 
of  water  and  sails  profuse  flowering  results.' 

3.  With  a  medium  water  and  salt  absorption  the  intensity  of  photosyn- 
thesis determines  whether  vegetative  growth  or  flowering  shall  occur.  When 
the  production  of  organic  substance  is  decreased,  e.g.,  in  blue  light,  vegetative 
growth  results,  and  when  it  is  increased,  flowering  occurs.' 

These  results  have  in  general  been  confirmed  by  the  observations 
and  experiments  of  others,  so  that  it  seems  to  be  a  well-estabUshed 
fact  that  the  development  of  flowers  depends  upon  dilTerent  meta- 
bolic conditions  from  those  which  determine  vegetative  growth. 
Observation  and  experiment  agree,  moreover,  in  indicating  that 
flowering  is  determined  by  the  accumulation  in  the  plant  of  organic 
substances  which,  because  of  insufficiency  of  water  and  salts,  are 
not  completely  transformed  into  metaboHcally  active  protoplasm 
or  its  products,  and  so  do  not  simply  produce  growth,  but  rather 
a  change  in  metabolic  conditions  in  the  direction  of  differentiation 
and  senescence. 

If  the  formation  of  a  new  vegetative  tip,  i.e.,  a  new  vegetative 
axis,  is  the  generalized  form  of  reproduction  in  the  flowering  plant 
(cf.  pp.  238-39),  then  there  can  be  no  doubt  that  the  flowering  is  a 
specialized  type  of  reproduction.  The  flower  certainly  shows  a 
much  higher  degree  of  differentiation  of  its  parts  than  does  the 
vegetative  axis.  Moreover,  the  metaboHc  conditions  which  favor 
flowering  are  conditions  which  cannot  arise  at  once  in  a  plant  indi- 
vidual beginning  its  development  and  dependent  upon  external 
sources  of  nutrition.  At  least  certain  stages  of  metabolic  history 
must  be  passed  through  before  the  plant  is  capable  of  being  brought 
into  the  flowering  condition.  Authorities  in  general  agree  that  a 
certain  amount  of  vegetative  growth  must  occur  before  the  plant 
can  be  induced  to  bloom.  In  other  words,  the  plant  must  appar- 
ently attain  a  certain  stage  of  development,  a  certain  physiological 
age,  before  flowering  is  possible.  But  this  stage  having  been 
attained,  the  further  metabolic  conditions  which  favor  flowering 
are  similar  in  character  to  those  which  bring  about  morphological 
difl"erentiation  and  senescence  in  animals,  for  the\-  consist  in  the 

'  Klebs,  '06,  pp.  105-6. 


374  SENESCENCE  AND  REJUVENESCENCE 

accumulation  of  inactive  or  relatively  inactive  organic  substances 
in  the  cells  and  consequently  a  decrease  in  metabolic  rate.  We  see 
also  that  such  internal  conditions  bring  about  a  higher  degree  of 
differentiation  in  the  plant  than  the  conditions  accompanying 
vegetative  growth.  Moreover,  the  parts  particularly  involved  in 
this  differentiation — the  inflorescence  axis  or  the  flower — do  not 
under  the  usual  conditions  undergo  any  further  vegetative  growth, 
but,  after  their  development  is  completed,  die  a  natural  death, 
and  in  many  cases  this  natural  death  involves  the  whole  plant, 
the  seeds  only  remaining  alive. 

The  evidence  seems  then  to  point  very  clearly  to  the  conclusion 
that  flowering  in  the  plant  is  characteristic  of  an  advanced  stage 
in  the  hfe  cycle — that  the  blooming  plant  is  physiologically  rela- 
tively old.  The  conditions  which  prevent  flowering  and  favor 
vegetative  growth  are  simply  such  as  keep  the  plant  in  a  relatively 
young  condition  by  preventing  the  accumulation  of  the  organic 
substances  and  bringing  about  repeated  vegetative  reproduction 
in  consequence  of  growth. 

It  may  seem  at  first  glance  that  the  metabolic  conditions  in  the 
flower  are  not  in  accord  with  the  conclusion  that  the  flower  is  the 
product  of  advanced  age  in  the  plant.  The  flower,  particularly  in 
its  earher  stages,  is  usually  the  seat  of  a  very  intense  respiratory 
activity  and  often  possesses  a  higher  rate  of  oxidation  than  any 
other  part  of  the  plant.'  If  blooming  is  a  feature  of  advanced  age 
and  if  rate  of  oxidation  is  in  any  way  associated  with  age,  it  would 
seem  that  we  ought  to  find  a  low  rate  of  oxidation  in  the  flower. 
Such  a  conclusion,  however,  ignores  completely  the  fact  that  the 
formation  of  the  flower  is  a  complex  reproductive  process  and 
unquestionably  involves  a  greater  or  less  degree  of  rejuvenescence 
which  appears  in  increased  respiratory  activity,  and  that  in  the 
formation  of  the  pollen  grains  in  the  anther  and  the  ovules  and 
embryo  sacs  in  the  ovary  extensive  reproduction  again  occurs. 
Moreover,  in  the  developing  flower  the  proportion  of  actively  grow- 
ing cells  to  the  total  weight  is  greater  than  in  the  vegetative  por- 
tions of  the  plant,  with  the  exception  of  the  embryonic  growing 

'See  A.  Maige,  '06,  '07;  G.  Maige,  '09,  '11,  and,  for  further  references,  Pfeffer, 
'97;  Nicolas,  '09. 


CONDITIONS  OF  GAMETE  FORMATION  375 

regions.     In   consequence   of   this   condition   the  flower  may   be 
expected  to  show  a  relatively  high  rate  of  respiration. 

The  accumulation  of  organic  material  and  the  relatively  low 
metabolic  rate  in  the  vegetative  parts  of  the  plant  are  probably 
factors  in  making  possible  the  high  rate  in  the  flower,  which  develops 
at  the  expense  of  the  nutritive  substances  in  other  parts.  The 
flower  is  a  new  individual  or  system  of  individuals,  which  arises 
under  conditions  of  low  metabolic  rate  in  other  parts,  and  such 
conditions  favor  the  establishment  in  it  of  a  high  rate  of  metabolism 
and  growth.  Evidently  the  flower  is  a  more  stable  structure  than 
most  of  the  vegetative  parts  of  the  plant  and  it  undergoes  rapid 
progressive  differentiation  and  aging.  These  characteristics  are 
also  doubtless  associated,  on  the  one  hand,  with  metabolic  condition 
of  advanced  age  in  other  parts  and,  on  the  other,  with  its  own  high 
metabolic  rate. 

In  most  flowers  the  rate  of  respiration  decreases  from  relatively 
early  stages  onward,  but  in  some  cases  it  undergoes  increase  or 
remains  almost  constant  up  to  the  time  of  opening.  These  differ- 
ences are  probably  associated  with  dift"erences  in  the  size  and 
amount  of  growth  of  the  ovary  and  its  contents  as  compared  with 
other  parts  of  the  flower.  It  was  suggested  in  the  preceding  chap- 
ter (pp.  349-50)  that  the  increase  in  rate  of  respiration  in  the  pistil 
during  its  development  is  connected  with  the  increasing  bulk  of  the 
growing  ovules  and  embryo  sacs  in  proportion  to  the  whole  pistil. 
Since  it  is  impossible  to  measure  the  respiratory  rate  of  single  gamc- 
tophytes  (pollen  grains  or  embryo  sacs)  or  gametes  during  their 
development,  the  available  data  on  rate  of  respiration  in  the  flower 
and  its  parts  are  incomplete  for  present  purposes.  In  the  case  of 
the  pistil  particularly  they  represent  measurements  of  rate  in  a 
complex  system  in  which  dift'erent  parts  attain  their  maximum 
activity  at  different  times  and  differ  in  amount  and  rate  of  growth 
in  different  cases.  Nevertheless,  so  far  as  the  data  are  applicable 
they  do  not  conflict  with,  but  rather  support,  the  view  that  the 
flower  is  a  product  of  relatively  advanced  physiological  age  in  the 

plant. 

In  those  cases  where  blooming  is  periodically  repeated  in  the  lilc 
of  the  plant,  as  in  perennials,  it  must  be  remembered  that  new 


376  SENESCENCE  AND  REJUVENESCENCE 

phytoids  are  concerned  and  that  each  period  represents  the  life 
history  of  a  generation  of  phytoids.  The  hfe  of  the  perennial, 
multiaxial  plant  is  not  comparable  to  the  life  of  an  individual 
animal,  but  is  made  up  of  innumerable  life  cycles  with  senescence 
and  death  of  the  more  highly  differentiated  parts  in  each  generation. 

From  this  standpoint  the  cases  of  premature  flowering  are  to  be 
regarded  simply  as  cases  of  prematurely  established  physiological 
conditions  resembling  those  which  usually  arise  only  after  a  con- 
siderable period  of  vegetative  activity.  It  is  impossible  to  con- 
sider these  cases  at  length,  and  in  many  of  them  the  determining 
conditions  have  not  been  analyzed.  One  interesting  case  recently 
recorded  by  Doposcheg-Uhlar  ('12)  may,  however,  be  mentioned. 
Bulbs  of  a  species  of  Begonia  could  be  made  to  produce  either  a 
vegetative  shoot  or  an  inflorescence  at  once  according  as  they  were 
allowed  to  produce  roots  or  not.  The  roots  provided  for  the 
entrance  of  water  and  salts  and  so  made  possible  the  transforma- 
tion of  the  organic  reserves  in  the  bulb  into  protoplasm,  and  under 
these  conditions  complete  rejuvenescence  to  the  vegetative  con- 
dition was  possible.  When,  however,  root  formation  did  not  occur, 
the  metabolic  conditions  in  the  cells  were  those  characteristic  of  an 
advanced  stage  of  the  life  cycle  under  ordinary  conditions  and 
growth  from  the  bulb  resulted  in  the  immediate  development  of 
the  highly  differentiated  flower  structure.  The  early  flowering  of 
various  other  plant  species  grown  from  bulbs  is  probably  to  be 
interpreted  in  the  same  way.  The  internal  conditions  in  such  cases 
are  those  of  relatively  advanced  age. 

Numerous  cases  of  the  transformation  of  an  inflorescence,  a 
flower  or  some  part  of  a  flower,  into  a  new  vegetative  axis  have 
been  recorded  by  various  authors  (see  pp.  246-47),  and  Klebs, 
Goebel,  and  others  have  induced  this  transformation  by  subjecting 
the  young  inflorescence  or  flower  to  external  conditions  favorable 
to  vegetative  growth.'  As  Goebel  ('08,  pp.  11 7-18)  suggests, 
these  cases  are  undoubtedly  to  be  interpreted  as  cases  of  return  to 
a  juvenile  stage.  The  external  conditions  have  made  dedift'eren- 
tiation  and  rejuvenescence  possible,  even  in  the  relatively  highly 
differentiated  flower. 

'  See  the  references  given  on  p.  246,  and  particularly  Klebs, '03,  '06. 


COXDITIONS  OF  GAMETE  FOR.MA  llO.V  377 

Proceeding  now  to  the  last  point  in  our  consideration,  the  devel- 
opment of  the  flower  is  preliminary  to  the  formation  of  the  gamete. 
The  gametophytes  develop  as  parts  of  the  flower  (see  pp.  320-22). 
the  pollen  grains  being  the  male,  the  embryo  sac  in  the  ovule  the 
female  gametophyte.  Although  these  gametophytes  are  much 
reduced  as  compared  with  those  of  the  mosses  and  ferns,  yet  their 
formation  in  the  seed  plants,  as  in  the  lower  forms,  is  unquestion- 
ably the  result  of  a  specialized  agamic  reproductive  process,  i.e., 
spore  formation.  The  gametophytes  arising  from  the  spore  are 
certainly  in  the  seed  plants  highly  specialized  organs  or  organisms. 
Their  development  differs  widely  in  the  two  sexes  and  in  both  is 
very  different  from  anything  else  in  the  development  of  the  plant 
(see  Figs.  140,  141,  pp.  320,  321). 

It  is  in  these  highly  specialized  organs,  or  individuals,  as  we 
choose  to  call  them,  that  the  gametes  are  formed.  The  whole 
history  of  the  plant  leading  up  to  the  formation  of  the  gametes 
is  a  history  of  specialization  and  differentiation  of  parts,  and  we 
have  therefore  every  reason  to  regard  the  gametes  as  among  the 
most  highly  speciaUzed  and  differentiated  cells  produced  by  the 
plant. 

CONDITIONS  OF  CONJUGATION  IN  THE  PROTOZO.A 

AccorcHng  to  Weismann  all  protozoa  are  potentially  germ  cells. 
Maupas  in  his  investigations  on  the  ciliates  reached  the  conciusii>n 
that  conjugation  results  from  internal  factors  which,  during  the 
period  of  agamic  reproduction,  bring  about  a  progressive  senescence 
of  the  stock  ending  in  death  unless  conjugation  occurs.  Conju- 
gation in  some  way  rejuvenates  the  animals  and  so  makes  possible 
a  new  series  of  agamic  generations.  But  the  investigations  of 
recent  years,  as  noted  in  chap,  vi,  have  forced  a  change  in  view.' 

On  the  one  hand,  the  breeding  experiments  of  Calkins,  Enriques, 
Woodruff,  and  Jennings  have  demonstrated  that  at  least  some  races 
of  Paramecium  and  other  ciliates  can  be  bred  agamically  for  hun- 
dreds or  thousands  of  generations,  and  probai)ly  indefmitely, 
without  the  occurrence  of  conjugation  and  without  loss  cl  vigor, 
provided  the  proper  conditions  are  maintained  in  the  medium. 

'  Among  the  more  important  references  are  those  given  in  the  footnotes  on  p.  136; 

see  particularly  Woodruff,  '14,  Jennings,  '12,  '13. 


378  SENESCENCE  AND  REJUVENESCENCE 

On  the  other   hand,  Enriques,  Jennings,  Woodruff,  Baitsell, 
and  others  have  shown  that  conjugation  may  be  induced  experi- 
mentally.    According  to  Jennings,  different  races  show  great  differ- 
ences in  their  capacity  or  tendency  to  conjugate,  some  conjugating 
every  few  weeks,  others  at  intervals  of  a  year  or  more,  or  not  at  all. 
But  in  those  races  which  conjugate  readily  conjugation  occurs, 
"not  as  a  result  of  starvation,  but  at  the  beginning  of  a  decline  in 
nutritive  conditions  after  a  period  of  exceptional  richness  that  has 
induced  rapid  multiplication.     At   the   time  of  conjugation   the 
animals  are  often  in  good  condition,  and  multipHcation  may  still 
be  in  progress"  (Jennings,  'lo,  p.  298).     As  regards  these  points 
Calkins  is  in  essential  agreement  with  Jennings.     In  his  experi- 
ments with  a  single  race  Zweibaum  found  that  conjugation  may  be 
induced  in  a  great  variety  of  ways,  provided  a  certain  nutritive 
condition  exists  in  the  animals.     This  condition  is  brought  about 
by  keeping  animals  which  have  been  richly  fed  for  some  weeks  in 
a  medium  with  less  food  and  then  removing  to  a  medium  containing 
almost  no   food.     Differences  in   the  methods  of   Jennings  and 
Zweibaum  may  be  due  to  differences  in  the  races  used  for  experi- 
ment, but  there  is  general  agreement  that  decreased  nutrition  favors 
the  occurrence  of  conjugation.     Woodruff  has  recently  brought 
about  conjugation  experimentally  in  the  Paramecium  culture  which 
has  been  bred  agamically  for  nearly  five  thousand  generations,  and 
Baitsell  has  also  found  that  the  occurrence  of  conjugation  in  other 
infusoria  can  be  experimentally  controlled. 

These  recent  investigators  agree  in  general  that  conjugation  is 
not  the  result  of  a  progressive  senescence,  and  so  does  not  represent 
the  end  of  the  life  history.  Calkins  and  Gregory  maintain  further 
"that  the  progeny  of  an  ex-conjugant  is  not  a  homogeneous  race, 
but  consists  of  differentiated  individuals  which  give  rise  to  pure 
lines,  some  of  which  conjugate,  others  do  not.  In  other  words, 
some  Paramecia  are  potential  germ  cells,  others  are  not."  Wood- 
ruff, however,  disputes  this  conclusion  and  holds  that  the  occur- 
rence or  non-occurrence  of  conjugation  depends  on  environmental 
conditions. 

In  chap,  vi  facts  are  cited  which  indicate  that  some  degree  of 
senescence  occurs  during  the  life  of  each  generation  and  some 


CONDITIONS  OF  GAMETE  FORMA'IloX  379 

degree  of  rejuvenescence,  at  least  in  the  cytoplasm,  in  each  agamic 
reproduction,  and  the  periodic  process  of  endomixis  and  the  repro- 
ductive rhythms  associated  with  it  were  interpreted  as  periods  of 
senescence,  death,  and  replacement  of  the  meganucleus.  Since 
Woodruff  and  Erdmann  ('14)  have  demonstrated,  not  only  that 
endomixis  occurs  periodically,  but  that  it  has  no  relation  to  the 
occurrence  of  conjugation,  we  must  conclude  that  the  progressive 
senescence  of  the  meganucleus  which  results  in  endomixis  is  not 
the  essential  factor  concerned  in  bringing  about  conjugation. 
Moreover,  since  conjugation  is  not  a  feature  of  an  internally 
determined  invariable  life  cycle,  but  is  rather  associated  with  and 
dependent  upon  certain  environmental  conditions,  at  least  to  a 
high  degree,  it  seems  probable  that  the  physiological  conditions  of 
conjugation  are  primarily  cytoplasmic  rather  than  nuclear,  for  the 
cytoplasm  is  more  affected  than  the  nucleus  by  the  environmental 
conditions. 

Since  cytoplasmic  rejuvenescence  occurs  with  each  agamic 
reproduction,  it  is  evident  that  the  physiological  age  of  the  cyto- 
plasm attained  in  each  generation  may  depend,  at  least  in  part, 
upon  the  frequency  of  reproduction.  With  abundant  food  and 
favorable  medium  the  reconstitution  associated  with  one  repro- 
duction is  scarcely  completed  before  another  reproduction  occurs. 
Under  such  conditions  the  degree  of  physiological  senescence  be- 
tween two  successive  fissions  must  be  less  than  when  the  interval 
between  reproductions  is  longer.  Consequently  certain  conditions 
which  retard  growth  and  agamic  reproduction,  but  which  are  not 
so  extreme  as  to  bring  about  either  complete  quiescence  or  star- 
vation and  reduction,  favor  the  attainment  of  a  more  advanced 
cytoplasmic  age  by  the  individuals  of  each  generation.  Under 
these  conditions  the  parts  continue  to  exercise  their  special  func- 
tions for  a  longer  period  before  undergoing  regressive  changes  in 
connection  with  reproduction,  and  the  advance  of  senescence  in 
each  generation  may  not  be  balanced  by  the  rejuvenescence 
occurring  in  each  reproduction,  so  that  progressive  cytoplasmic 
senescence  of  the  race  may  occur.  We  need  not  expect,  however, 
to  find  conspicuous  morphological  differences  between  such  ani- 
mals and  those  which  are  growing  and  reproducing  rapidly.     The 


38o  SENESCENCE  AND  REJUVENESCENCE 

differences  can  at  most  be  merely  those  between  physiologically  older 
and  younger  individuals  both  of  which  have  attained  the  adult  form, 
and  in  organisms  as  simple  as  the  cihates  would  be  more  readily 
distinguishable  physiologically  than  morphologically.  But  so  far 
as  I  am  aware,  this  point  has  not  been  considered  by  most  students 
of  protozoa.  One  author,  Prowazek  ('lo),  has  stated  that  when 
cultures  of  Colpidium  are  prevented  from  dividing  by  insufhcient 
nutrition,  they  rapidly  become  old.  In  his  cultures,  however,  the 
animals  were  evidently  starved,  for  they  underwent  reduction  in 
size  to  a  considerable  extent  and  their  susceptibility  to  atropin 
underwent  a  marked  increase.  These  changes  in  size  and  suscepti- 
bihty  suggest  that  these  cultures  were  undergoing  reduction  and 
increase  in  rate  of  metaboHsm  in  consequence  of  partial  starvation 
(cf.  chap,  vii)  instead  of  undergoing  senescence.  Nutrition  seems 
to  have  been  insufhcient  in  this  case  to  permit  senescence  to  occur; 
for  that  the  food  should  have  been  at  least  sufficient  to  prevent 
decrease  in  size. 

But  the  important  point  is  that  those  conditions  which  favor  a 
progressive  senescence  are  the  conditions  which  favor  conjugation. 
The  facts  from  this  point  of  view  suggest  simply  that  under  con- 
ditions which  favor  rapid  agamic  reproduction  the  animals  have 
no  opportunity  to  attain  maturity  because  of  the  frequent  recon- 
stitution  and  rejuvenescence.  When  agamic  reproduction  is 
retarded  or  inhibited,  maturity  is  very  soon  attained  and  conju- 
gation occurs. 

The  occurrence  of  endomixis  indicates,  as  I  have  pointed  out, 
that  the  meganucleus  undergoes  senescence  in  spite  of  agamic 
reproduction.  If,  at  the  time  when  the  meganucleus  is  approach- 
ing death,  the  cytoplasm  is  physiologically  young  and  in  good 
metabolic  condition,  then  apparently  endomixis  and  recovery  with- 
out conjugation  occur,  but  if,  at  this  time,  the  cytoplasm  is  also  in 
a  condition  of  advanced  physiological  senescence,  then  probably 
the  physiological  conditions  for  conjugation  are  present,  and  if  con- 
jugation is  impossible,  death  may  result.  According  to  this  view, 
endomixis  results  from  progressive  senescence  of  a  single  speciahzed 
organ,  the  meganucleus,  and  conjugation  from  the  senescence  of 
both  meganucleus  and  cytoplasm. 


CONDITIONS  OF  GAMETE  FORMA'IIOX  381 

If  senescence  is  essentially  a  decrease  in  rate  of  metabolism,  the 
stage  of  maturity  must  possess  a  lower  rate  of  metabolism  than  the 
stage  in  which  agamic  reproduction  is  occurring.  While  I  have  not 
as  yet  made  a  systematic  study  of  the  changes  in  susceptibility  of 
ciliates  with  changes  in  medium  and  other  conditions,  certain 
differences  in  susceptibility  observed  in  a  culture  of  Colpidium  are 
of  some  interest  in  this  connection.  This  culture  was  at  first  under- 
going very  rapid  agamic  reproduction  and  the  small,  recently 
divided  individuals,  as  well  as  most  of  those  in  late  stages  of  division, 
were  more  susceptible  to  cyanide  than  the  larger,  older  individuals. 
In  the  course  of  a  few  days  an  acute  epidemic  of  conjugation 
occurred  in  the  culture,  and  fissions  almost  ceased:  conjugation 
was  confined  to  the  larger  individuals  of  the  culture.  At  this  stage 
the  small  animals  were  most  susceptible,  the  large,  non-conjugating 
animals  less  susceptible,  and  the  conjugating  pairs  least  susceptible 
of  all.  The  low  susceptibility  of  the  conjugants  indicates  that  they 
possess  a  lower  metabohc  rate  and  so  are  physiologically  older  than 
the  other  members  of  the  culture. 

These  experiments  suggest  that  the  occurrence  of  conjugation 
is  associated  with  the  attainment  of  a  certain  physiological  age.  a 
condition  of  maturity,  with  a  relatively  low  rate  of  metabolism. 
If  this  conclusion  is  correct,  we  must  consider  the  question  of  the 
influence  of  external  conditions  upon  the  attainment  of  this  ma- 
turity: is  it  possible  to  accelerate  or  retard  its  occurrence  through 
cultural  or  other  environmental  conditions  ?  It  is  not  to  be 
expected  that  a  sudden  decrease  in  rate  of  metabolism  induced  by 
external  conditions  will  bring  about  a  normal  maturitv  in  a  vcrx- 
young  individual:  such  a  change  would  simply  retard  or  inhibit  its 
development.  But  when  development  has  reached  a  certain  stage 
and  the  organism  is  approaching  maturity,  then  it  is  very  probable 
that  a  slight  decrease  in  metabolic  rate,  externally  induced,  may  be 
sufficient  in  many  cases  to  bring  about  or  accelerate  the  change 
which  under  constant  external  conditions  would  have  occurred  much 
more  slowly.  Some  of  the  chemical  agents  which  Zweibaum  and 
others  have  used  to  induce  conjugation  may  perhaps  act  in  this  way. 

As  regards  the  diff'erent  capacity  or  tendency  of  different  races 
to  conjugate,  which  has  been  discussed  by  Jennings,  Woodruff,  and 


382  SENESCENCE  AND  REJUVENESCENCE 

Calkins,  it  is  possible  at  present  only  to  point  out  certain  probable 
factors  concerned.  In  the  first  place,  the  rate  and  course  of  indi- 
vidual senescence  or  rejuvenescence  under  a  given  complex  of  con- 
ditions is  probably  different  in  different  races  of  Paramecium  and 
other  forms,  and  the  rate  and  course  of  individual  senescence  or 
rejuvenescence  in  a  given  race  may  differ  under  different  conditions. 
Differences  of  this  kind  also  appear  to  some  extent  in  planarians. 
In  Planaria  vclata  the  course  of  the  age  cycle  depends  upon  the 
character  of  the  food  (see  pp.  169-75).  With  some  kinds  of  food 
progressive  senescence  from  generation  to  generation  occurs  and 
in  a  few  generations  death  results,  while  with  others  rejuvenes- 
cence and  senescence  balance  each  other  in  each  generation. 
Doubtless  similar  relations  exist  in  Paramecium  and  other  ciliates 
between  character  of  food,  rate  of  senescence  in  each  generation, 
and  degree  of  rejuvenescence  in  each  reproduction.  And  it  is  not 
at  all  improbable  that  various  other  factors  besides  nutrition,  e.g., 
many  chemical  agents,  may  influence  the  rate,  degree,  and  course 
of  development,  senescence,  and  rejuvenescence. 

Whether,  as  Calkins  believes,  some  races  of  Paramecium  and 
other  ciliates  are  not  even  potentially  capable  of  conjugation  can 
be  determined  only  by  extensive  investigation,  and  then  only  with 
a  certain  degree  of  probability.  It  is  of  course  conceivable  that 
in  organisms  with  great  capacity  for  agamic  reproduction  the 
capacity  to  attain  gametic  maturity  may  not  be  realized  under 
ordinary  conditions  (see  chap,  x),  but  as  yet  we  have  no  adequate 
basis  for  maintaining  that  the  potentiahty  is  absent  in  such  cases. 

In  the  higher  animals  a  definite  sequence  of  events  is  a  funda- 
mental characteristic  of  the  Hfe  cycle,  and  it  seems  not  wholly 
logical  to  maintain  that  a  sequence  is  entirely  absent  in  the  simpler 
forms.  We  can  scarcely  doubt  that  an  individual  Paramecium, 
continuing  to  live  without  reproduction  and  with  sufficient  food 
for  maintenance  in  a  constant  medium  which  does  not  inhibit 
metabolism,  will  undergo  certain  more  or  less  definite  changes,  and 
will  show  a  Hfe  history.  And  it  seems  probable  that  if  these  changes 
proceed  sufficiently  far  without  interruption  by  reproduction  or 
change  in  external  conditions,  the  individual  may  attain  maturity — 
the  physiological  condition  in  which  conjugation  occurs — or  may 


CONDITIONS  OF  GAMETE  FORMATIOX  383 

even  die  of  old  age.  But  the  more  readily  agamic  rcproduclion 
occurs  in  consequence  of  either  internal  or  external  factors,  the  less 
likely  is  the  life  history  of  the  individual  to  attain  its  later  stages. 
In  the  case  of  the  protozoa  the  question  of  progressive  race 
senescence  has  occupied  the  minds  of  most  investigators  to  the 
exclusion  of  individual  senescence.  Apparently,  however,  the 
solution  of  the  whole  problem  is  to  be  found  in  the  relation  between 
individual  senescence  and  rejuvenescence  under  different  conditions. 
If  progressive  senescence  in  a  race,  ending  in  conjugation  or  death, 
does  not  occur  in  a  race  bred  agamically,  it  is  not  because  the 
individuals  do  not  undergo  senescence,  but  rather  because  the 
cytoplasmic  senescence  in  each  generation  is  compensated  by 
rejuvenescence  in  each  agamic  reproduction  and  because  senescence 
of  the  meganucleus  is  compensated  by  the  process  of  nuclear  reor- 
ganization which  Woodruff'  and  Erdmann  have  called  endomixis. 

CONDITIONS  OF  GAMETE  FORMATION  IN  THE  MULTICELLULAR  AXIilALS 

Our  knowledge  concerning  the  physiological  conditions  which  de- 
termine the  formation  of  gametes  in  the  lower  multicellular  animals 
is  as  yet  very  fragmentary.  As  regards  many  forms  we  do  not  even 
know  whether  sexual  maturity  occurs  once  or  periodically  in  the 
life  cycle,  or  whether  its  appearance  is  merely  a  reaction  to  external 
conditions.  Observation  of  the  animals  in  nature  seems  to  indicate 
clearly  enough  that  in  general  the  formation  of  gametes  occurs  only 
when  a  period  of  vegetative  growth,  with  or  without  agamic  repro- 
duction, is  approaching  or  has  reached  its  end.  In  the  case  of  the 
fresh-water  hydra  considerable  experimental  work  has  been  done.' 
and  most  authors  agree  that  low  temperature  determines  sexual 
maturity,  although  different  species  appear  to  differ  to  some  extent 
as  regards  the  effective  temperatures.  Nussbaum  maintains  that 
starvation  or  at  least  decrease  in  nutrition  is  the  essential  factor, 
but  other  authors  do  not  agree  with  him.  'J'hese  results  do  not 
afford  us  any  very  deep  insight  into  the  physiology  of  gamete 
formation.  They  merely  indicate  that  a  relatively  low  rale  of 
metabolism  favors  or  even  determines  gamete  formation,  but 
whether  gamete  formation  ever  occurs  without  the  aid  of  external 

'R.  Hertwig, '06;  Krapfenbauer, '08;  Frischolz, '09;  Nussbaum, 'og;   Koch, '11. 


384  SENESCE^XE  AND  REJUVENESCENCE 

factors  which  decrease  metabolism  we  do  not  know.  It  may  be 
that  such  processes  as  budding  and  the  replacement  of  differ- 
entiated old  cells  by  young  cells  from  the  interstitial  tissue  prevent 
progressive  development  in  hydra  beyond  a  certain  point  under 
the  usual  conditions,  in  which  case  low  temperatures  by  decreasing 
the  rate  of  metabolism  may  bring  about  essentially  the  same  changes 
that  would  occur  in  further  development  determined  by  internal 
factors.  In  many  if  not  in  all  of  the  coelenterates,  however,  there 
are  indications  that  the  formation  of  gametes  is  associated  with  an 
advanced  stage  of  the  life  cycle. 

One  of  the  most  interesting  cases  is  that  of  certain  jelly-fishes 
or  medusae  belonging  to  the  family  MargeHdae  (Chun,  '96;  Braem, 
'08) .  These  medusae  reproduce  agamically  by  budding,  and  buds 
arise  in  a  definite  order  upon  the  proboscis  and  develop  from  the 
ectoderm  alone  instead  of  from  both  body  layers,  as  do  other  coelen- 
terate  buds.  The  young  medusa  gives  rise  to  these  buds,  but  as  it 
grows  older  sex  organs  begin  to  appear  from  the  same  body  layer 
and  in  the  same  region  as  the  buds  and  sometimes  in  place  of  them. 
Fig.  196  shows  the  proboscis  of  one  of  these  medusae  on  which 
both  buds  and  ovaries  containing  eggs  are  present.  After  the  sex 
organs  once  appear  the  buds  gradually  cease  to  form  and  only 
gametes  are  produced  in  later  stages. 

In  these  medusae  the  same  region  and  layer  of  the  body  and, 
so  far  as  we  can  determine,  cells  of  exactly  the  same  character,  give 
rise  in  the  younger  animal  to  agamic  buds  and  in  later  stages  to 
gametes.  Very  evidently  the  physiological  condition  of  these  cells 
undergoes  change  during  the  life  history  of  the  animal.  Braem 
regards  this  case  as  indicating  that  the  agamic  buds  as  well  as  the 
gametes  arise  from  germ  plasm,  but  it  seems  rather  to  indicate  that 
gametes  as  well  as  agamic  buds  may  arise  from  cells  which  are 
functional,  more  or  less  specialized  parts  of  the  organism,  and  that 
the  gametes  are  more  highly  specialized  cells  and  arise  later  in  the 
life  history  than  those  which  develop  into  buds. 

As  regards  the  planarian  worms  a  few  facts  are  at  hand.  Atten- 
tion has  already  been  called  (pp.  99,  125)  to  the  fact  that  Planaria 
dorotocephala  is  not  known  to  reproduce  sexually  at  all  in  the  locahty 
where  I  have  collected  material.     But  in  stocks  which  are  kept  in 


CONDITIONS  OF  GAMETE  FORMATION' 


385 


the  laboratory  under  uniform  conditions,  provided  with  abundant 
food  and  prevented  from  undergoing  fission,  the  animals  often  con- 
tinue to  grow  until  they  are  fully  twice  as  large  as  the  largest  found 
under  natural  conditions,  and  a  considerable  number  of  these  very 
large  animals  develop  the  hermaphroditic  sexual  organs  character- 
istic of  the  species,  become  sexually  mature,  and  lay  eggs.     Often 


Fig.  196. — Manubrium  of  female  Lizzia  (jelly-fish),  showing  agamic  buds  and 
eggs:  in  addition  to  the  four  large  eggs,  0,  those  regions  which  are  occupied  by  dis- 
tinctly difJerentiated  ovarial  cells  are  indicated  by  drawing  in  cell  outlines  and  nuclei; 
in  the  dotted  regions  are  cells  which  may  become  either  buds  or  ovarian  cells:  roman 
numerals  I,  III,  IV,  V,  VII,  indicate  buds  in  the  order  of  their  formation,  bud  I  having 
already  become  free  and  buds  II  and  VI  being  on  the  other  side  of  the  manubrium; 
the  point  *  indicates  the  position  where  the  eighth  bud  should  appear.  From  Bracm, 
'08. 

sexually  mature  animals  can  be  made  to  undergo  fission  simply  by 
transferring  them  to  another  perfectly  clean  aquarium  without 
slime  on  its  walls,  and  when  the  level  of  fission  is  anywhere  near  t  he 
openings  of  the  sexual  ducts,  w^hich  lie  a  short  distance  behind  the 
mouth,  the  openings  and  all  the  terminal  organs  disappear. 

The  very  low  susceptibility  of  the  sexually  mature  animals  to 
cyanides,  as  compared  with  that  of  the  largest  animals  in  nature. 


386  SENESCENCE  AND  REJUVENESCENCE 

indicates  that  physiologically  they  are  very  much  older  than  the 
latter.  In  consequence  of  continued  feeding  and  growth  and  the 
absence  of  the  reconstitutional  changes  connected  with  fission, 
these  animals  have  evidently  attained  a  stage  of  development  which 
is  not  reached  by  the  animals  in  nature. 

The  conditions  in  nature  which  prevent  the  animals  from 
attaining  the  later  stages  of  development  and  sexual  maturity  are 
less  abundant  food  and  consequently  greater  activity,  which  in 
turn  determines  more  frequent  fission,  so  that  the  animals  are 
almost  continuously  undergoing  reconstitution.  Moreover,  the 
animals  are  subjected  more  or  less  periodically  to  periods  of  partial 
starvation.  Insufficiency  of  food  may  arise  from  the  rapid  increase 
in  numbers  of  the  animals  by  fission  during  the  summer,  perhaps 
also  from  the  slow  reproduction  of  the  food  animals  in  winter. 
These  two  facts,  fission  and  repeated  partial  starvation,  contribute 
to  keep  the  animals  physiologically  young  and  so  prevent  them 
from  attaining  the  age  and  physiological  condition  in  which  sexual 
maturity  occurs. 

Planaria  maculata  becomes  sexually  mature  in  some  locahties 
and  not,  or  only  very  rarely,  in  others  (Curtis,  '02).  In  the  latter 
locahties  the  factors  which  prevent  the  occurrence  of  sexual  ma- 
turity are  undoubtedly  the  same  as  those  which  produce  the  result 
in  P.  dorotoccpliala,  i.e.,  repeated  fission  and  periodical  or  occasional 
partial  starvation. 

In  a  stock  of  P.  maculata  kept  in  the  laboratory  I  found  that 
sexually  mature  individuals,  after  egg  laying,  lose  the  sexual  organs 
and  undergo  a  considerable  reduction  in  size.  During  this  period 
they  take  httle  or  no  food,  but  after  a  time  begin  once  more  to  feed 
and  grow,  and  if  growth  is  rapid  they  may  reproduce  agamically, 
while  if  it  is  slow  they  may  in  some  cases  become  sexually  mature 
again  without  passing  through  any  period  of  agamic  reproduction. 

The  dift'erences  in  susceptibihty  of  the  animals  at  these  different 
periods  indicate  that  the  sexually  mature  stages  are  physiologically 
older  than  others,  and  that  after  egg  laying  they  undergo  a  consider- 
able degree  of  rejuvenescence  during  the  reduction,  and  once  more 
begin  to  undergo  senescence  when  they  begin  to  feed.  Whether 
they  remain  asexual  or  become  sexually  mature  depends  on  the 


CONDITIONS  OF  GAMETE  FORMATION  387 

amount  and  uniformity  of  the  food  supply  and  the  rate  of  growth. 
There  is  no  question  that  in  P.  maculata,  as  well  as  in  P.  dorolo- 
cepliala,  sexual  maturity  represents  a  condition  of  greater  physio- 
logical age  than  the  asexual  stage. 

The  case  of  P.  velata  is  somewhat  different.  Under  the  con- 
ditions where  it  is  usually  found  in  nature,  as  well  as  in  the  labora- 
tory', this  form  unquestionably  grows  old,  ceases  to  feed,  and 
undergoes  fragmentation  in  each  generation  without  becoming 
sexually  mature.  Apparently  sexual  reproduction  has  no  place  in 
the  life  cycle  of  this  species.  If  it  were  not  for  the  fact  that  the 
animal  stops  feeding  and  ceases  to  grow  before  fragmentation 
occurs  we  might  believe  that  the  Ufe  cycle  of  the  individual  is  sim- 
ply interrupted  as  in  P.  dorotocephala  and  in  many  plants  by  the 
agamic  reproduction,  but  as  a  matter  of  fact  the  period  of  develop- 
ment and  growth  is  apparently  completed  before  fragmentation 
begins.  Thus  far  it  has  not  been  possible  to  induce  sexual  maturity 
experimentally  in  this  species.  It  seems  probable,  however,  that 
certain  of  the  feeding  experiments  already  described  afford  a  clue 
to  the  understanding  of  this  case.  It  was  pointed  out  that  the 
length  of  the  growth  period  and  the  amount  of  growth  before 
fragmentation  differ  very  widely  with  different  foods.  In  other 
words,  the  rate  of  senescence  differs  according  to  character  of  food. 
This  suggests  the  possibiHty  that  with  certain  foods  growth  might 
continue  and  fragmentation  be  delayed  until  attainment  of  the 
stage  of  sexual  maturity,  but  only  further  experiment  can  throw 
light  upon  the  question. 

As  regards  the  parasitic  groups  of  flatworms,  the  flukes  and  the 
tapeworms,  there  can  be  no  doubt  that  formation  of  gametes  and 
sexual  reproduction  is  characteristic  of  an  advanced  stage  in  the 
life  of  the  individual.  Such  parasites  are  subjected  to  but  little 
change  in  external  conditions,  especially  those  living  in  the  bodies 
of  mammals,  and  yet  they  pass  through  a  definite  life  history,  ending 
in  the  development  of  gametes  and,  following  this,  the  death  of  the 
individual.  In  some  of  the  flukes  the  number  of  larval  generations 
between  the  egg  and  the  development  of  the  sexual  organs  may 
differ  according  to  external  factors,  but  the  relation  between 
sexual   maturity   and   relatively  advanced   age   is   unmistakable. 


388  SENESCENCE  AND  REJUVENESCENCE 

In  other  animal  groups  in  which  agamic  reproduction  is  a  more 
or  less  characteristic  feature  of  the  life  cycle — certain  families  of 
annelids,  the  bryozoa,  and  the  tunicates — it  is  in  general  true 
that  agamic  precedes  gametic  reproduction  in  the  life  history,  and 
in  some  of  these  forms,  notably  in  certain  annelids,  agamic  repro- 
duction may  apparently  continue  indefinitely  under  certain  con- 
ditions without  the  attainment  of  sexual  maturity. 

Among  the  higher  invertebrates,  and  among  the  vertebrates, 
the  definite  character  and  internal  determination  of  the  life  history 
become  in  most  cases  even  more  apparent.  In  many  forms,  as  in 
most  of  the  insects,  development  ends  in  a  single  period  of  gametic 
production  followed  by  death.  In  many  other  forms,  after  ma- 
turity is  once  attained,  the  production  of  gametes  is  periodic  or 
continuous  and  the  animal  may  live  for  a  long  time  and  may  also 
undergo  extensive  growth,  as  do  most  of  the  mollusks  after  the 
first  period  of  sexual  maturity.  In  such  cases  growth,  as  well  as 
gamete  production,  appears  to  be  periodic,  and  the  formation  of 
gametes  follows,  at  least  in  most  cases,  the  growth  period. 

Periodicity  of  this  sort  in  the  organism  is  commonly  associated 
with  periodicity  in  the  environment,  e.g.,  with  seasonal  or  other 
periodic  changes.  The  environmental  periodicity  may  determine 
slight  alterations  of  senescence  and  rejuvenescence  as  perhaps  in 
the  case  of  the  mollusks,  where  growth  periods  ending  with  or 
followed  by  gamete  formation  occur  or  in  other  cases  the  activity 
of  the  sexual  organs  may  be  directly  influenced  by  nutritive  con- 
dition, temperature,  etc. 

That  the  vertebrates  pass  through  a  definite  developmental 
history,  with  sexual  maturity  as  a  comparatively  late  stage,  and 
that  this  history  is  primarily  determined  by  factors  within  the 
organism  rather  than  environmental  conditions  is  sufficiently 
evident.  Here  agamic  reproduction  does  not  occur,  except  in  a 
few  cases  in  early  embryonic  stages,  and  the  life  history  is  without 
the  complications  which  arise  in  lower  forms  to  prevent,  balance, 
or  retard  progressive  development.  Even  among  the  vertebrates, 
however,  the  appearance  of  sexual  maturity  may  be  hastened  or 
retarded  by  the  character  and  amount  of  the  food  and  by  various 
other  environmental  conditions.     The  tadpoles  of  frogs  and  sala- 


CONDITIONS  OF  GAMETE  FORMATION  389 

manders,  for  example,  may  be  made  to  undergo  metamorphosis 
into  the  adult  form  at  a  very  small  size  or  to  attain  giantism  without 
metamorphosis  by  controlling  the  character  of  the  food  (Guder- 
natsch,  '12,  '14;  Romeis,  '14),  and  their  development  may  be  modi- 
fied in  various  other  ways.  Even  in  man  the  age  in  years  at  which 
sexual  maturity  occurs  varies  somewhat  widely  with  climatic  and 
other  factors.  But  none  of  these  facts  indicate  anything  more  than 
that  a  certain  physiological  condition  of  the  organism  may  be 
attained  sooner  or  later  according  to  the  nature  of  the  environment. 

In  various  species  among  both  invertebrates  and  vertebrates 
cases  of  premature  sexual  maturity  may  occur  while  the  animal  is 
still  morphologically  a  larva,  as  in  the  so-called  axolotl  form  of 
certain  salamanders;  or  after  sexual  maturity  in  the  larval  stage 
the  sex  organs  may  disappear  and  the  animal  undergo  meta- 
morphosis to  the  adult  form,  after  which  new  sex  organs  arise 
and  a  second  period  of  sexual  maturity  occurs,  as  in  certain 
ctenophores. 

Evidently  the  sex  organs  may  mature  and  produce  gametes 
at  various  stages  of  morphological  development,  but  we  know 
nothing  of  the  physiological  conditions  in  these  cases.  In  the  light 
of  the  facts  already  cited,  however,  it  is  probable  that,  whatever 
the  morphological  stage  at  which  sexual  maturity  occurs,  certain 
physiological  conditions  must  exist  in  the  organism  which  make  its 
appearance  possible  and  that  these  are  conditions  which  ordinarily 
arise  relatively  late  in  development.  In  other  words,  the  cases 
of  premature  sexual  maturity  are  probably  cases  of  accelerated 
physiological  senescence. 

PARTHENOGENESIS  AND  ZYGOGENESIS 

In  several  of  the  invertebrate  groups,  viz.,  the  rotifers,  the  clado- 
cera  among  the  Crustacea,  and  the  plant  lice  and  related  families 
among  the  insects,  the  eggs  of  a  single  individual  or  of  successive 
generations  differ  in  behavior,  some  developing  parthenogenically 
into  females  or  males,  and  others  zygogenically,  i.e.,  requiring 
fertihzation  for  development. 

Within  recent  years  members  of  the  crustacean  group  of 
cladocera,    the    daphnids,    have    been    the    subject   of   extensive 


390  SENESCENCE  AND  REJUVENESCENCE 

investigation  along  these  lines/  and  while  different  authorities  are 
not  as  yet  in  full  agreement,  evidence  which  points  to  a  definite 
conclusion  is  accumulating. 

It  is  well  known  that  the  daphnid  females  produce  three  kinds 
of  eggs,  parthenogenic  eggs  which  produce  females,  parthenogenic 
eggs  which  produce  males,  and  zygogenic  eggs  which  produce 
females.  Both  the  female-  and  male-producing  parthenogenic 
eggs  develop  at  once  and  are  commonly  known  as  "summer  eggs." 
The  zygogenic  eggs,  on  the  other  hand,  are  surrounded  by  a  thick 
shell  and  hatch  only  after  a  quiescent  period  which  often,  but  not 
necessarily,  coincides  with  the  winter  season,  hence  they  are  known 
as  "winter  eggs."  The  problem  to  which  attention  has  been 
chiefly  directed  is  that  of  the  relative  importance  of  external  and 
internal  factors  in  determining  the  production  of  these  three  kinds 
of  eggs.  Weismann  believed  that  a  fixed  cycle  of  generations 
determined  by  inheritance  existed  in  each  species  quite  independ- 
ently of  external  factors;  according  to  this  view  a  certain  number 
of  generations  of  parthenogenic  females  were  produced,  then  males 
developed  from  parthenogenic  eggs  and  zygogenic  eggs  were  pro- 
duced, which  after  a  quiescent  period  developed  into  parthenogenic 
female-producing  females,  and  these  began  the  cycle  anew. 

Later  investigators  have  found  that  the  cycle  of  generations  is 
far  from  being  hereditarily  fixed  and  that  it  can  be  greatly  modified 
by  external  factors.  Under  certain  conditions,  e.g.,  with  high  tem- 
perature and  abundant  nutrition,  parthenogenic  reproduction  may 
continue  indefinitely.  Other  conditions,  such  as  low  temperature 
and  lack  of  food,  favor  the  production  of  males  and  zygogenic  eggs. 
In  general,  males  and  zygogenic  eggs  are  produced  under  similar 
conditions.  Moreover,  Woltereck  has  found  that  after  producing 
males  the  females  may  again  begin  to  produce  females  partheno- 
genically  without  producing  winter  eggs,  and  the  same  change  may 
occur  even  after  the  production  of  winter  eggs.  Kuttner  showed, 
however,  that  the  cycle  of  generations  may  occur  independently 
of  change  in  external  conditions. 

'  Some  of  the  more  important  papers  are  the  following:  Issakowitsch,  '06,  '08; 
Kuttner,  '09;  Langhans,  '09;  Papanicolau,  '100,  '10b,  '11;  von  Scharfenberg,  '10; 
Strohl,  '07,  '08;  Weismann,  '80;  Woltereck,  '09,  '11. 


CONDITIONS  OF  GAMETE  FORMATION 


391 


Woltereck's  extensive  investigations,  together  with  the  evidence 
from  the  work  of  others,  seem  to  show  very  clearly  that,  while 
differences  exist  in  different  races  and  species,  nevertheless  a  cyclical 
change  affecting  the  character  of  the  eggs  produced  does  occur  in 
these  animals  independently  of  external  factors,  although  it  may 
be  modified  by  temperature,  nutrition,  and  chemical  constitution 
of  the  medium  in  which  the  animals  live.  Woltereck  divides  the 
cycle  into  three  periods,  the  first  including  the  early  generations  of 
females  following  the  winter  eggs.  These  females  are  predomi- 
nantly parthenogenic  and  female-producing,  at  least  until  late  in 
life,  and  external  factors  have  no  effect  on  the  character  of  the  eggs. 
After  this  follows  a  second  period  in  which  external  conditions 
determine  to  a  very  large  extent  whether  parthenogenic  eggs  pro- 
ducing females,  or  parthenogenic  eggs  producing  males  and  zygo- 
genic  eggs  are  produced,  and  finally  a  third  period  occurs  in  which 
parthenogenic  eggs  producing  males  and  female-producing  zygogenic 
eggs  appear  independently  of  external  conditions. 

Von  Scharfenberg  and  Papanicolau  found  that  a  change  in  egg 
character  occurred,  not  only  in  the  course  of  successive  generations, 
but  also  in  the  course  of  single  generations,  i.e.,  the  eggs  produced 
early  in  the  life  of  a  female  are  more  Hkely  to  develop  partheno- 
genically  into  females  and  those  produced  later  in  Hfe  into  males 
or  to  be  zygogenic  winter  eggs.  In  the  earlier  generations  of  a 
cycle  the  male-producing  and  zygogenic  eggs  appear  later  in  the 
life  of  the  individuals,  in  later  generations  earlier.  Moreover, 
the  same  three  periods  appear  more  or  less  clearly  in  the  repro- 
ductive cycle  of  the  single  females  as  in  the  cycle  of  generations. 

This  reproductive  cycle  appearing  both  in  single  individuals 
and  in  successive  generations  is  in  certain  respects  analogous  to  the 
cycle  of  agamic  and  gametic  reproduction  in  many  of  the  lower 
animals.  In  the  early  stages  of  the  cycle  the  daphnids,  although 
producing  what  we  call  eggs,  are  really  reproducing  agamically, 
since  the  eggs  develop  parthenogenically,  but  in  later  generations, 
as  well  as  later  in  the  Hfe  of  the  individual,  they  become  sexually 
mature,  and  males  and  females  appear  and  the  eggs  require  ferti- 
lization. There  seems  to  be  a  progressive  change  in  physiological 
condition  in  these  animals,  both  individually  and  in  successive 


392  SENESCENCE  AND  REJUVENESCENCE 

generations,  which  corresponds  to  the  aging  and  the  attainment  of 
sexual  maturity  in  other  forms.  The  parthenogenic  female- 
producing  egg  is  apparently  characteristic  of  the  young  animal 
and  the  earher  generations  in  a  cycle,  the  parthenogenic  male- 
producing  egg  and  the  zygogenic  female-producing  egg  of  a  more 
advanced  age  in  the  individual  and  in  the  generations.  Richard 
Hertwig  ('12)  in  discussing  these  facts  says:  "  It  is  therefore  possible 
to  speak  in  a  double  sense  of  an  aging  of  the  daphnids  and  of  a 
change  in  the  constitution  of  the  eggs  determined  by  it." 

Woltereck  has  found  that  an  individual  may  pass  through 
more  than  one  of  these  reproductive  cycles.  Even  after  producing 
winter  eggs,  females  may  again  pass  through  a  labile  period  in 
which  the  character  of  the  eggs  can  be  influenced  by  external  con- 
ditions and  still  later  attain  a  condition  in  which  the  eggs  are 
parthenogenic  and  female-producing  in  spite  of  external  conditions. 
In  other  words,  they  become  physiologically  young  again.  But  it 
has  been  shown  in  earher  chapters  that  such  rejuvenescence  occurs 
in  many  forms.  In  the  case  of  the  daphnids  it  does  not  proceed 
as  far  as  in  many  of  the  lower  animals,  for  these  may  lose  their 
sexual  organs  entirely  and  return  to  reproduction  by  budding  or 
fission,  while  in  the  daphnids  we  find  only  a  return  from  the  produc- 
tion of  zygogenic  to  the  production  of  parthenogenic  eggs. 

As  regards  the  rotifers,  in  certain  species  of  which  partheno- 
genesis and  bisexuality  exist,  the  various  investigators''  still  differ 
widely  in  their  opinions  as  to  the  determining  factors.  The  effect- 
ive factor  in  determining  parthenogenesis  and  bisexuality  is  accord- 
ing to  Maupas  temperature,  and  according  to  Nussbaum  nutrition, 
while  Punnett  finds  that  neither  of  these  external  factors  is  con- 
cerned, but  that  the  character  of  the  eggs  is  hereditarily  determined. 
Whitney  regards  the  age  of  the  family,  that  is,  the  position  in  the 
cycle  of  generations,  as  the  important  factor,  although  he  admits 
the  influence  of  external  conditions.  And,  finally,  Shull  has  demon- 
strated the  influence  ef  external  factors  in  the  environmental 
medium,  apparently  of  chemical  nature,  but  believes  that  internal 
factors  are  also  involved.     With  such   differences  of  opinion  it 

Olaupas,  '91;  M.  Nussbaum,  '97;  Punnett,  '06;  Shull,  '10,  'iia,  'ii5,  '12; 
Whitney,  '07,  '12a,  '12b. 


CONDITIONS  OF  GAMETE  F0R:\IATI0N  393 

seems  at  least  probable  that  internal  physiological  conditions, 
which  are  not  yet  clearly  recognized,  are  the  real  determining 
factors,  and  that  the  various  external  factors  merely  modify  their 
action.  As  Woltereck  ('11)  has  pointed  out,  there  is  every  reason 
to  believe  that  the  relation  between  parthenogenesis  and  bisexu- 
ahty  is  essentially  the  same  in  the  rotifers  as  in  the  daphnids. 

Parthenogenesis  and  bisexuality  are  also  found  among  the 
plant  lice  and  various  other  related  forms  among  the  hemiptera. 
In  these  cases,  as  in  the  daphnids,  bisexuality  appears  later  in  the 
cycle  than  parthenogenesis,  but  concerning  the  influence  of  external 
conditions  in  modifying  the  usual  course  of  events,  our  knowledge 
is  fragmentary.  Low  temperature  or  lack  of  food  may  apparently 
at  times  induce  bisexuality,  as  in  the  daphnids.  All  that  we  know 
suggests  that  in  this,  as  in  other  cases,  bisexuality  is  a  feature 
of  more  advanced  age  than  parthenogenesis,  and  that  the  aging 
may  be  accelerated  or  retarded,  perhaps  reversed,  by  external 
conditions. 

The  parthenogenic  egg  is  apparently  a  less  highly  specialized, 
physiologically  younger  cell  than  the  egg  requiring  fertihzation. 
Morphologically  it  is  less  highly  differentiated,  at  least  in  many 
cases,  than  the  zygogenic  egg  (see  pp.  342-46),  and  when  isolated 
from  the  parent  body  it  is  capable  of  developing  at  once  without 
fertilization  (cf.  pp.  406-8).  If  such  eggs  are  produced  by  animals 
in  the  earlier  stages  of  their  adult  hfe  history  or  by  the  earlier 
generation  of  a  cycle,  we  are  forced  to  the  conclusion  that  the  germ 
cells  undergo  differentiation  and  aging  like  the  rest  of  the  body. 
In  short,  the  egg  produced  by  the  older  organism  is  itself  older 
and  more  highly  specialized  than  that  produced  by  a  younger. 

The  physiological  character  of  the  action  of  external  conditions 
in  modifying  the  eggs  can  at  present  only  be  surmised.  Woltereck 
suggests  that  the  differences  in  the  eggs  are  due  to  differences  in  the 
intensity  of  assimilation  in  the  ovary,  high  intensity  determining 
parthenogenic  female-producing  eggs  and  low  intensity  bisexual 
eggs.  A  decrease  in  intensity  of  assimilation  is,  however,  a  char- 
acteristic feature  of  senescence  and  may  result  from  internal  as 
well  as  from  external  conditions.  Apparently  the  external  factors, 
whatever  the  exact  mechanism  of  their  action,  either  accelerate, 


394  SENESCENCE  AND  REJUVENESCENCE 

retard,  or  reverse  the  life  cycle  of  the  whole  animal  and  so  affect  the 
character  of  the  eggs,  or  else  they  alter  conditions  in  the  ovaries 
so  that  eggs  are  isolated  from  the  parent  organism  earher  or  later 
in  their  development. 

If  the  external  conditions  decrease  the  general  metabohsm,  they 
may  bring  about  physiological  conditions  which  would  arise  without 
their  action  in  more  advanced  stages  of  senescence,  but  if  their 
eflfect  is  to  increase  metabolism,  they  may  make  the  animal  some- 
what younger  physiologically  by  increasing  breakdown  and  elimi- 
nation, or  they  may  at  least  retard  or  inhibit  senescence.  In  this 
manner  the  character  of  the  eggs  may  be  influenced  through  the 
physiological  condition  of  the  whole  animal. 

It  is  probable,  however  that  the  physiological  age  and  condition 
of  the  egg  do  not  necessarily  correspond  in  all  cases  to  the  physio- 
logical age  of  the  egg-producing  organism.  Under  certain  conditions, 
such  as  abundant  nutrition  or  high  temperature,  the  development  of 
successive  eggs  may  be  so  rapid  that  each  egg  is  forced  down  the 
ovarian  tubules  and  isolated  before  its  growth  is  completed,  even 
though  the  animal  itself  is  physiologically  old.  Such  an  egg  must 
be  physiologically  younger  than  one  which  undergoes  more  growth 
before  isolation.  Probably  the  action  of  external  factors  in  deter- 
mining parthenogenesis  and  bisexuahty  is  sometimes  of  this  charac- 
ter, and  a  high  rate  of  egg  production  results  in  younger  eggs,  a 
low  rate  of  egg  production  in  older  eggs. 

Summing  up,  this  point  of  view  seems  to  afford  a  basis  for 
reconcihng  the  apparently  conflicting  data,  and  for  further  analytic 
investigation.  The  parthenogenic  egg  in  the  daphnids  and  rotifers 
is  apparently  physiologically  younger  and  less  highly  differentiated 
than  the  zygogenic;  the  physiological  age,  both  of  the  individual 
and  of  the  race,  and  probably  also  the  rate  and  conditions  of  egg 
production,  are  factors  in  determining  whether  parthenogenic  or 
zygogenic  eggs  shall  be  produced;  and,  finally,  external  factors  act 
by  accelerating,  retarding,  or  reversing  the  course  of  the  life  history 
in  the  individual  or  race,  or  by  influencing  the  rate  and  other 
conditions  of  egg  production  in  the  ovary. 

It  seems  to  be  definitely  determined  that  among  the  bees  the 
males  arise  from  parthenogenic  eggs,  the  females  from  fertilized 


CONDITIONS  OF  GAMETE  FORMATION  395 

eggs,  as  Dzierzon  maintained  more  than  sixty  years  ago.'  The 
queen  bee  is  apparently  capable  of  producing  drone  eggs  at  any 
time,  or  at  least  repeatedly,  during  her  life.  It  is  conceivable  that 
all  eggs  produced  by  the  queen  are  potentially  parthenogenic  and 
so  male-producing,  but  that  when  fertilized  they  produce  females 
(see  pp.  344-45),  but  if  the  parthenogenic  eggs  are  physiologically 
different  from  the  zygogenic  in  this  case,  it  seems  probable  that  the 
former  are  at  least  slightly  younger  than  the  latter  when  they 
leave  the  ovary.  If,  as  suggested  above,  not  only  the  physio- 
logical age  of  the  animal, but  the  conditions  in  the  ovary  determining 
the  rate  of  egg  production — the  abundance  of  nutrition,  etc. — are 
factors  in  the  determination  of  parthenogenic  and  zygogenic  eggs, 
old  queens  may  produce  parthenogenic  or  young  queens  zygogenic 
eggs  under  certain  conditions.  Only  under  fairly  constant  external 
conditions  could  a  definite,  fixed  relation  between  physiological 
condition  of  the  egg  and  physiological  age  of  the  parent  be  expected. 

In  certain  of  the  parasitic  flatworms — the  digenetic  trematodes 
— two  or  more  larval  generations  occur  between  the  fertilized  egg 
and  the  adult  stage.  The  first  of  these  larval  generations  arises 
from  the  egg  as  a  single  individual  which  contains  within  its  body 
certain  cells  known  as  germ  cells.  Each  of  these  germ  cells  develops 
within  the  parent  body  into  a  larval  individual  of  the  second  genera- 
tion, and  in  many  cases  these  larvae  likewise  contain  germ  cells 
which  give  rise  to  a  third  larval  generation :  sometimes  the  process 
may  continue  still  farther,  but  in  any  case  the  final  larval  generation 
undergoes  transformation  into  a  single  adult  individual  and  becomes 
sexually  mature. 

The  germ  cells  in  the  bodies  of  these  trematode  larvae  have 
commonly  been  regarded  as  eggs,  and  the  development  of  the  second 
and  following  larval  generations  as  cases  of  parthenogenesis.  The 
observation  of  Gary  ('09)  that  these  germ  cells  resemble  partheno- 
genic eggs  in  giving  rise  to  a  single  polar  body  before  beginning 
development  gives  further  support  to  this  view.  If  these  cells  are 
actually  parthenogenic  eggs  or  approach  such  eggs  in  their  charac- 
teristics, their  appearance  during  or  immediately  after  the  embryonic 

'The  latest  studies  on  the  subject,  Nachtsheim,  '13,  Armbruster,  '13,  give  an 
extensive  bibliography. 


396  SENESCENCE  AND  REJUVENESCENCE 

period  seems  to  conflict  with  the  conclusion  reached  in  the 
present  chapter  that  the  formation  of  gametes  is  a  feature  of 
relatively  late  stages  in  the  life  history  of  the  individual.  This 
conflict,  however,  is  apparent  rather  than  real.  Each  larval  genera- 
tion has  a  life  history  of  its  own  not  essentially  different  from  that 
of  other  animals:  during  this  period  it  undergoes  progressive  dift'er- 
entiation  and  growth,  but  the  rate  of  growth  decreases  and  the 
larva  finally  dies,  apparently  of  old  age.  I  have  determined  the 
changes  in  susceptibility  to  cyanides  of  two  of  the  larval  generations 
of  certain  species  and  have  found  that  a  marked  and  rapid  decrease 
in  susceptibility  occurs  in  each  generation  and  that  the  early  stages 
of  each  generation  show  a  much  higher  susceptibiHty  than  the  late 
stages  of  the  preceding  generation.  This  means  that  each  genera- 
tion undergoes  a  rapid  senescence  and  that  rejuvenescence  occurs 
during  each  reproduction,  but  there  is  some  evidence  that  progressive 
senescence  from  generation  to  generation  also  occurs  to  some  extent. 
During  the  earlier  stages  of  the  life  of  a  larva  the  cells  which 
later  become  germ  cells  undergo  division  and  so  increase  in  number, 
but  they  do  not  become  mature  and  begin  independent  development 
into  new  individuals  until  a  relatively  late  larval  stage  of  larval 
life  is  reached.  The  period  of  reproduction  through  the  germ  cells 
is  in  fact  a  feature  of  advanced  age  in  the  life  of  the  larva.  The  cells 
resemble  eggs  in  possessing  a  low  metabolic  rate  before  beginning 
development  because  they  are  parts  of  a  physiologically  old  body, 
and  it  is  probable  that  the  occurrence  of  a  maturation  division  with 
the  formation  of  a  polar  body  is  connected  with  this  condition  (see 
pp.  353-56).  What  we  commonly  cafl  the  life  history  of  these 
worms  is  then  in  reality  a  series  of  life  histories  with  alternating 
periods  of  senescence  and  rejuvenescence.  Each  period  of  senes- 
cence is  accompanied  in  its  later  stages  by  reproduction  through 
cells  which  resemble  parthenogenic  eggs  more  or  less  closely,  but 
only  in  advanced  age  of  the  final  generation,  the  adult  form,  do 
sexual  maturity  and  fertilization  occur.  Certain  other  points  in 
these  life  histories  are  of  interest  in  connection  with  the  problem  of 
the  fife  cycle,  but  this  brief  consideration  is  perhaps  sufficient  to 
show  that  the  pecuhar  larval  reproduction  of  these  species  is  a 
feature  of  advanced  age  Hke  gametic  reproduction  in  other  forms. 


CONDITIONS  OF  GAMETE  FORMATION  397 

CONCLUSION 

It  is  apparently  true  for  both  animals  and  plants  that  the  pro- 
duction of  gametes  is  associated  with  certain  internal  conditions 
which  are  characteristic  of  an  advanced  physiological  age.  But 
since  the  course  of  the  age  cycle  may  be  accelerated,  retarded,  or 
reversed  by  the  action  of  external  factors,  the  formation  of  gametes 
in  the  lower  organisms,  where  the  influence  of  external  factors  is 
relatively  great,  may  often  appear  to  be  largely  dependent  upon 
these  external  factors.  Not  only  is  gamete  production  a  feature 
of  relatively  advanced  age,  but  in  some  cases  the  physiological 
age  of  the  egg — parthenogenic  or  zygogenic  character — apparently 
depends  to  some  extent  on  the  physiological  age  of  the  parent. 

The  association  of  gamete  formation  with  advanced  physio- 
logical age  is  a  fact  of  great  importance,  for  it  indicates  that  the 
"germ  plasm"  is  an  integral  physiological  part  of  the  organism 
and  that  the  formation  of  the  gametes  is  the  final  stage  of  a  period 
of  progressive  development  in  the  reproductive  cells.  In  the  earlier 
stages  of  the  hfe  history  of  the  organism  isolated  cells  or  cell  masses 
may  react  to  isolation  by  dedifferentiation  and  reconstitution  to  a 
new  individual,  i.e.,  agamic  reproduction  occurs.  The  partheno- 
genic egg  is  apparently  a  cell  which  has  undergone  a  considerable 
degree  of  differentiation  as  a  gamete,  but  has  not  lost  the  capacity 
to  react  to  isolation  by  dedifferentiation  and  reconstitution.  And. 
finally,  the  zygogenic  gamete  has  attained  a  stage  of  differentiation 
and  senescence  in  which  it  is  no  longer  capable  alone  of  reacting  to 
isolation,  but  can  undergo  dedifferentiation  and  reconstitution  only 
when  fertiHzation  occurs.  If  there  are  any  cells  in  the  organism 
which  do  not  contain  "undifferentiated  germ  plasm,"  the  gametes 
certainly  seem  to  be  among  those  cells. 

REFERENCES 

Armbruster,  L. 

1913.     "  Chromosomenverhaltnisse    bei    der    Spermatogencse    soliliirer 
Apiden  {Osmia  corniita  Latr.),"  Arcli.f.  Zclljorsch..  XI. 

Bary,  A.  DE. 

1878.     "tJber  apogame  Fame  und  die  Erscheinung  der  Apogamie  im  All- 
gemeinen,"  Bot.  Zcituiig,  XXXVL 


398  SENESCENCE  AND  REJUVENESCENCE 

Benecke,  W. 

1906.     "Einige  Bemerkungen  iiber  die  Bedingungen  des  Bliihens  und 
Fruchtens  der  Gewachse,"  Bot.  Zcitung,  LXIV,  Abt.  II, 
Braem,  F. 

1908.  "Die  Knospung  der  Margeliden,  ein  Bindeglied  zwischen  ge- 
schlechtlicher  und  ungeschlechtlicher  Fortpflanzung,"  Biol.  Cen- 
tralbl.,  XXMII. 

Cary,  L.  R. 

1909.  "The  Life  History  of  Diplodiscus  temporatus  Stafford,"  Zool. 
Jahrbiicher;  Abt.  f.  Anat.  u.  Out.,  XXVlll. 

Chun,  C. 

1896.  "Atlantis;  Biologische  Studien  iiber  pelagische  Organismen:  I, 
Die  Knospungsgesetze  der  proliferierenden  Medusen,"  Biblio- 
theca  Zool.,  VII,  19. 

Curtis,  W.  C. 

1902.  "The  Life  History,  the  Normal  Fission  and  the  Reproductive 
Organs  of  Planaria  maculata,"  Proc.  of  the  Boston  Soc.  of  Nat. 
Hist.,  XXX. 

DiELS,  L. 

1906.  J ugendformen  und  Bliitenreife  im  Pflanzenreich.     Berlin. 
Doposcheg-Uhlar,  I. 

191 2.     "Friihblute  bei  Knollenbegonien,"  Flora,  CIV. 

Farlow,  W.  G. 

1874.     "An   Asexual    Growth   from   the   Prothallus   of   Pteris  cretica," 
Quart.  Jour,  of  Micr.  Sci.,  XIV. 
Farmer,  J.  B.,  and  Digby,  L. 

1907.  "Studies  in  Apospory  and  Apogamy  'n  Ferns,"  Annals  of  Bot., 
XXI. 

Fischer,  A. 

1905.  "tJber  die  Bliitenbildung  in  ihrer  Abhangigkeit  vom  Licht  und 
die  bliitenbildenden  Substanzen,"  Flora,  XCIV. 

Frischolz,  E. 

1909.     "Zur  Biologie  von  Hydra,''  Biol.  CentralbL,  XXIX. 

GOEBEL,  K. 

1908.  Einleitung  in  die  experimentelle  Morphologic  der  Pflanzen.     Leipzig. 

GUDERNATSCH,  J.  F. 

191 2.     "Feeding  Experiments  on  Tadpoles:   I,  The  Influence  of  Specific 

Organs  Given  as  Food  on  Growth  and  Differentiation,"  Arch. 

f.  Entwickelungsmech. ,  XXXV. 
1914.     "Feeding  Experiments  on  Tadpoles:   II,  A  Further  Contribution 

to  the  Knowledge  of  Organs  with  Internal  Secretion,"  Am.  Jour. 

of  Anat.,  XV. 


CONDITIONS  OF  GAMETE  FORMATION  399 

Heim,  C. 

1896.     "  Untersuchungen  an  Famprothallien,"  Flora,  LXXXII. 
Hertwig,  R. 

1906.     "tJber  Knospung  und  Geschlechtsentwickelung  von  Hvdra  fusca," 

Biol.  Centralbl.,  XXVI. 
191 2.     "tJber    den    derzeitigen    Stand    des    Sexualitatsproblems    nebst 
eigenen  Untersuchungen,"  Biol.  Centralbl.,  XXXII. 

ISSAKOWITSCH,  A. 

1906.     "  Geschlechtsbestimmende  Ursachen  bei  den  Daphniden,"  Arch. 

f.  mikr.  Anal.,  LXIX. 
1908.     "Es  besteht   eine  zyklische   Fortpflanzung  bei  den   Daphniden 

aber  nicht  im  Sinne  Weismanns,"  Biol.  Centralbl.,  XXVIII. 

Jennings,  H.  S. 

1910.  "What  Conditions  Induce  Conjugation  in  Paramecium?"  Jour,  of 
Exp.  ZooL,  IX. 

1912.  "Age,  Death  and  Conjugation  in  the  Light  of  Work  on  Lower 
Organisms,"  Pop.  Sci.  Monthly,  June. 

1913.  "The  Effect  of  Conjugation  in  Paramecium,"  Jour,  of  Exp.  ZooL, 
XIV. 

JOST,  L. 

1908.     Vorlesungen  iiber  PJlanzenphysiologie:   II.  Auflage.     Jena. 

Klebs,  G. 

1903.  W illkiirliche  Entwicklungsanderungen  bei  Pflanzen.     Jena. 

1904.  "Uber  Probleme  der  Entwickelung,"  Biol.  Centralbl.,  XXI\'. 
1906.  Uber  kilnstliche  Metamorphosen.     Stuttgart. 

Koch,  W. 

191 1.  "Uber  die  Geschlechtsbildung  und  den  Gonochorismus  von  Hydra 
fusca,  Uber  die  geschlechtliche  Differenzierung  und  den  Gono- 
chorismus von  Hydra  fusca,"  Biol.  Centralbl.,  XXXI. 

Krapfenbauer,  a. 

1908,  Einwirkimg  der  Existenzbedingungen  auf  die  Fortpflanzung  von 
Hydra.     Inaugural  Dissertation.     Miinchen. 

KUTTNER,  O. 

1909.  "Untersuchungen  iiber  Fortpflanzungsverhaltnisse  und  Vererbung 
bei  Cladoceren,"  Internat.  Rev.  d.  gcs.  Hydrobiol.  u.  Uydrogr.,  II. 

Langhans,  V.  H. 

1909.  "Experimentelle  Untersuchungen  zu  Fragen  der  Fortpflanzung. 
Variation  und  Vererbung  bei  Daphniden,"  Vcrhandlungcn  d. 
deutsch.  zool.  Gesell. 

LoEW,  0. 

1905.  "Zur  Theorie  der  bliitenbildenden  Stoffe,"  Flora,  XCI\'. 


400  SENESCENCE  AND  REJUVENESCENCE 

Maige,  a. 

1906.     "Sur  la  Respiration  de  la  fleur,"  Compt.  rend.  Acad.  Sci.,  CXLII. 
IQ07.     "Recherches  sur  la  respiration  de  la  fleur,"  Rev.  gen.  de  hot.,  XIX. 

Maige,  G. 

1909.     "Recherches  sur  la  respiration  de  Tetamine  et  du  pistil,"  i?CT.  gen. 

de  hot.,  XXI. 
191 1.     "Recherches  sur   la    respiration   des  differentes   pieces   florales," 

Ann.  des  sci.  nat.;  Boi.,  (9).  XIV. 

Maupas,  E. 

1891.     "Sur  la  Determinisme  de  la   sexualite   chez   VHydatina   senta," 
Compt.  rend.  Acad.  Sci.,  CXIII. 

MoBius,  M. 

1897.     Beit  rage  zur  Lehre  von  der  Fortpflatizung  der  Gewdchse.     Jena. 

Nachtsheim,  H. 

1913.     "  Cytologische    Studien    liber    die    Geschlechtsbestimmung    bei 
der  Honigbiene  {Apis  mellifica  L.),"  Arch.  f.  Zellforsch.,  XI. 

Nicolas,  G. 

1909.     "Recherches  sur  la  respiration  des  organes  vegetatifs  des  plantes 
vasculaires,"  Aim.  des  sci.  nat.  Bot.,  (9).  X. 

NUSSBAUM,  M. 

1897.     "Die  Entstehung  des  Geschlechtes  bei  Hydatina  senta,"  Arch.  f. 
mikr.  Anat.,  XLIX. 

1909.  "tjber  Geschlechtsbildung  bei  Polypen,"  Arch.  J.  d.  ges.  Physiol., 
CXXX. 

Papanicolau,  G. 

1910a.  "tJber  die  Bedingungen  des  sexuellen  Differenzierung  bei  Daph- 

niden,"  Biol.  Centralbl.,  XXX. 
19106.   "Experimentelle    Untersuchungen    iiber    die    Fortpflanzungsver- 

haltnisse  der  Daphniden,"  Biol.  Centralbl.,  XXX. 
1911.     Anhang.     Biol.  Centralbl.,  XXXI. 

Pfeffer,  W. 

1897.     Pflanzcnphysiologie,  Zweite  Auflage,  I,  Band. 

Prowazek,  S. 

1910.  "  Gif twirkung   und    Protozoenplasma,"    Arch.  J.   Protistenkunde, 
XVIII. 

PUNNETT,  R.  C. 

1906.     "Sex-Determination  in  Hydatina,  with   Some  Remarks  on  Par- 
thenogenesis," Proc.  Roy.  Sac.  B.,  LXXVIII. 


CONDITIONS  OF  GAMETE  FORMATION  401 

ROMEIS,    B. 

1914.  "Experimentelle  Untersuchungen  uber  die  Wirkung  innersekrcto- 
rischer  Organe:  II,  Der  Einfluss  von  Thyreoidea-  und  Thymus- 
fiitterung  auf  das  Wachslum,  die  Entwicklung  und  die  Regenera- 
tion," Arch.f.  Ent-ivickclungsmcch.,  XL,  XLI. 

SCHARFEXBERG,  U.  VON. 

1910.     "Studien  und  Experimente  iiber  die  Eibildung  und  den  Genera- 

tionszyklus  von  Daphnia  magna,'"  Internal.  Rev.  d.  ges.  Uydrobiol. 

II.  Hydrogr.     Biol.  Supplement. 
Shull,  a.  F. 

1910.     ''Studies  in  the  Life  Cycle  of  Hydatina  scnta:  I,  Artificial  Control 

of  the  Transition  from  the  Parthenogenetic  to  the  Se.xual  Method 

of  Reproduction,"  Jour,  of  Exp.  Zool.,  MIL 
1911a.  "Studies,  etc.:    II,  The  Role  of  Temperature,  of  the  Chemical 

Composition  of  the  Medium  and  of  Internal  Factors  upon  the 

Ratio  of  Parthenogenetic  to  Sexual  Forms,"  Jour,  of  Exp.  Zool.,  X. 
191 16.   "The  Effect  of  the  Chemical  Composition  of  the  Medium  on  the 

Life  Cycle  of  Hydatina  scnta,"  Biochem.  Bull.,  I. 
1912.     "Studies,  etc.:    Ill,  Internal  Factors  Influencing  the  Proportion 

of  Male  Producers,"  Jour,  of  Exp.  Zool.,  XII, 
Strohl,  H. 

1907.     "Die  Biologie  von  Polyphemus  pcdiculus  und  die  Generations- 

zyklen  der  Cladoceren,"  Zool.  .inz.,  XXXII. 
190S.     "Polyphemusbiologie,   Cladocereneier  und   Kernplasmarelation," 

Intcrnat.  Rev.  d.  ges.  Hydrobiol.  u.  Hydrogr.,  I. 

VOCHTING,  H. 

1893.  "tjber  den  Einfluss  des  Lichtes  auf  die  Gestaltung  und  Anlage 
der  Bliithen,"  Jahrhiicher  f.  wiss.  Bot.,  XXV\ 

WEISiL-VNN,  A. 

1880.     "Beitrage  zur  Naturgeschichte  der  Daphnoiden,  VII,"  Zeitschr. 
f.  wiss.  Zool.,  XXXIII. 
Whitney,  D.  D. 

1907.  "Determination  of  Sex  in  Hydatina  senta,"  Jour,  of  Exp.  Zool.,  V. 
1912a.  "  'Strains'  in  Hydatina  senta,"  Biol.  Bull.,  XXII. 

191 26.  "Weak  Parthenogenetic  Races  of  Hydatina  senta  Subjected  to  a 
Varied  Environment,"  Biol.  Bull.,  XXIII. 
Winkler,  H. 

1908.  "tJber  Parthenogenesis  und  Apogamie  im  Pflanzenrciche,"  Pro- 
gressus  rei.  bot.,  11. 

Woltereck,  R. 

1909.  "Weitere  experimentelle  Untersuchungen  iiber  .\rlvcrandcrung' 
speciell  iiber  das  Wesen  quantitativer  .-Vrtunterschiede  bei  Daph- 
niden,"  V erhandlungen  d.  deutsch.  zool.  Gescll. 


402  SENESCENCE  AND  REJUVENESCENCE 

WOLTERECK,  R. 

191 1,     "tjber  Veranderung  der  Sexualitat  bei  Daphniden,"  Internal.  Rev. 
d.  ges.  Hydrobiol.  n.  Hydrogr.,  IV. 

Woodruff,  L.  L. 

1914.     "On  So-called  Conjugating  and  Non-conjugating  Races  of  Para- 
mecium,''^ Jour,  of  Exp.  ZooL,  XVI. 

Woodruff,  L.  L.,  and  Erdmann,  Rhoda. 

1914.     "A  Normal  Periodic  Reorganization  Process  without  Cell  Fusion 
in  Paramecium,"  Jour,  of  Exp.  ZooL,  XVII. 

WORONIN,  HeLENE. 

1908.     "Apogamie  und  Aposporie  bei  einigen  Farnen,"  Flora,  XCVIII. 


CHAPTER  XV 

REJUYTNESCENCE  IN  EMBRYONIC  AND  LARVAL 
DEVELOPMENT 

If  the  gametes  are  physiologically  old  cells,  rejuvenescence  must 
occur  during  embryonic  development,  for  the  organism  when  it 
begins  its  active  independent  life  at  the  end  of  the  embr>-onic 
period  is  certainly  very  much  younger  in  every  respect  than  the 
gametes  before  fertilization.  It  now  remains  to  consider  the 
evidence  bearing  upon  this  point.  This  evidence  is  chiefly  zoo- 
logical rather  than  botanical,  for  in  most  of  the  plants  the  early 
embryonic  stages  cannot  readily  be  isolated  for  experimental 
purposes. 

THE  EFFECT  OF  FERTILIZATION 

To  attempt  any  consideration  of  the  problem  of  fertihzation 
itself  would  lead  us  too  far  afield;  moreover,  no  well-established 
and  generally  accepted  theory  of  fertilization  has  as  yet  emerged 
from  the  great  mass  of  often  conflicting  experimental  data  and 
opinions.  It  is  the  efTect  of  fertilization  rather  than  the  process 
itself  with  which  we  are  primarily  concerned. 

Whatever  the  nature  of  the  process,  it  is  a  self-evident  fact  that 
the  union  of  the  two  gametes  is  usually  the  starting-point  of  a 
new  period  of  activity  and  change  in  the  resulting  cell.  It  is  true 
that  in  some  cases  among  both  plants  and  animals  fertihzation  is 
followed  after  a  short  period  of  activity  by  a  quiescent  period,  but 
we  know  that  in  certain  of  these  cases  the  cessation  of  activity  is 
due  to  incidental  or  external  factors,  such  as  the  presence  of  an 
impermeable  shell  or  envelope  of  some  sort  which  cuts  off  the  supply 
of  oxygen  or  water,  or  otherwise  interferes  with  dynamic  activity 
until  it  is  removed  in  one  way  or  another,  or  gamete  formation  may 
occur  at  seasons  of  the  year  or  under  external  conditions  which 
retard  or  inhibit  metabolic  activity.  In  the  delayed  germination 
of  plant  seeds,'  in  the  quiescent  encysted  periods  of  certain  protozoa 

'  See,  for  example,  Crocker,  '06,  '07,  '09;  and  references  to  literature  in  these 
papers. 

403 


404  SENESCENCE  AND  REJUVENESCENCE 

after  union  of  the  gametes,  and  in  the  cessation  of  development  of 
the  "winter  eggs"  of  flatworms,  rotifers,  Crustacea,  and  insects, 
the  presence  of  shells  or  envelopes  of  some  sort  is  undoubtedly  the 
chief  factor  in  retarding  or  inhibiting  the  metabolic  activity.  Even 
in  those  animal  eggs  which,  like  some  seeds,  must  before  they  will 
hatch  be  subjected  to  certain  external  conditions,  such  as  freez- 
ing temperature  or  desiccation,  or  in  the  case  of  Branchipus,  the 
fairy  shrimp,  apparently  to  both,  there  is  good  reason  to  beHeve 
that  the  effect  of  these  conditions  in  altering  or  disintegrating  the 
egg  envelope  is  much  more  important  than  any  effect  which  they 
may  have  upon  the  protoplasm  itself.  These,  however,  are  cases 
of  the  cessation  of  development  rather  than  of  its  failure  to  begin. 

There  are  some  cases  where  gametic  union  does  not  result  in  a 
period  of  increased  activity  and  where  internal  rather  than  external 
factors  seem  to  be  responsible.  Jennings  ('13),  for  example,  has 
found  that  in  Paramecium  the  effects  of  conjugation  are  by  no 
means  uniform,  for  many  of  the  ex-conjugants  show  decreased  rather 
than  increased  activity  and  some  die,  while  others  do  exhibit  an 
increased  rate  of  growth  and  division.  It  is  probable  that  this  lack 
of  uniformity  in  the  results  of  gametic  union  is  connected  with  the 
fact  that  the  body  and  the  gamete  are  the  same  cell.  Different 
individuals  become  specialized  in  different  directions  and  the 
physiological  effect  of  gametic  union  must  vary  widely,  for  in  some 
cases  the  two  protoplasms  are  incompatible  in  some  way,  or  a  sum- 
mation of  their  physiological  defects  occurs,  while  in  others  the 
result  is  the  opposite.  In  the  multicellular  organisms,  however, 
where  the  gametes  develop  as  speciahzed  parts  of  the  body  more  or 
less  remote  from  the  influence  of  factors  external  to  the  organism, 
their  course  of  development  and  consequently  the  effects  of  their 
union  are  much  more  definite  and  uniform,  but  even  here  the  results 
of  gametic  union  may  vary  to  some  extent,  although  increased 
dynamic  activity  following  union  is  the  usual  result. 

There  are  in  fact  very  few  exceptions  to  the  rule  that  gametic 
union  is  followed  by  increased  dynamic  activity,  and  it  is  probable 
that  most,  if  not  all,  of  these  exceptions  will  prove  to  be  apparent 
rather  then  real.  We  may  say  then  with  Loeb  that  fertilization 
in  some  way  saves  the  Ufe  of  the  gametes.     If  the  gametes  are  highly 


REJUVENESCENCE  IN  EMBRYO  AND  LARVA  405 

differentiated,  physiologically  old  cells,  approaching  death,  an 
increase  in  dynamic  activity  can  scarcely  mean  anything  else  than 
the  beginning  of  a  period  of  rejuvenescence  and  dedifferentiation. 
The  increase  in  the  dynamic  activity  of  the  sea-urchin  egg  after 
fertilization  has  been  determined  in  various  ways  by  various  inves- 
tigators.' Lyon  found  that  the  susccptibiUty  of  the  eggs  to  cyanide 
was  greater  after  than  before  fertilization.  Measurements  of  the 
oxygen  consumption  of  the  egg  of  the  Neapolitan  sea-urchin 
{Strongylocentrotus  lividus)  by  Warburg  showed  that  after  fertiliza- 
tion the  oxygen  consumption  was  between  six  and  seven  times  as 
great  as  before,  and  Loeb  and  Wasteneys  found  that  in  an  American 
sea-urchin  {Arhacia  punctulata)  the  fertihzed  egg  consumed  three 
to  four  times  as  much  oxygen  as  the  unfertilized.''  In  a  study  of 
heat  production  in  the  sea-urchin  egg  Meyerhof  finds  the  heat 
production  per  hour  between  four  and  five  times  as  great  in  fer- 
tihzed as  in  unfertiHzed  eggs. 

In  the  starfish  egg,  however,  according  to  Loeb  and  Wasteneys 
('12),  the  oxygen  consumption  is  about  the  same  before  and  after 
fertilization.  This  dift'erence  in  behavior  between  starfish  and  sea- 
urchin  eggs  is  undoubtedly  connected,  as  Loeb  ('11)  suggested, 
with  the  fact  that  in  the  starfish  the  extrusion  of  the  eggs  from  the 
ovaries  into  sea-water  starts  the  maturation  divisions,  while  in  the 
sea-urchin  maturation  has  occurred  and  the  egg  is  quiescent  when 
the  sperm  enters  it.  But  the  unfertilized  starfish  egg  dies  very 
soon  unless,  according  to  Loeb,  its  oxidation  processes  are  inhibited 
by  lack  of  ox>'gen  or  by  cyanide.^  As  a  matter  of  fact,  the  starfish 
egg  is  almost  a  parthenogenic  egg,  as  Mathews  ('01)  has  shown. 
By  experimental  means  its  development  can  readily  be  initiated 
without  fertilization.  But,  left  to  itself,  it  is  apparently  not  quite 
able  to  begin  normal  development;  something  goes  wrong  and 
death  soon  follows.  The  unfertilized  sea-urchin  egg,  on  the  other 
hand,  which  remains  almost  quiescent  after  extrusion  from  the 

'Loeb, '10;  LoebandWasteneys, '10, '11;  Lyon, '02;  Meyerhof, '11;  Warburg, 
'oS, '10. 

^  There  are  certain  sources  of  error  in  the  method  used  for  determining  oxygen 
consumption  which  make  it  possible  that  these  values  are  too  high,  but  that  an  increase 
occurs  cannot  be  doubted. 

3  Loeb,  '11;  Loeb  and  Wasteneys,  '12. 


4o6  SENESCENCE  AND  REJUVENESCENCE 

ovary  and  does  not  begin  development  until  the  sperm  enters,  may 
live  for  a  week  or  more.  The  death  of  the  unfertiHzed  starfish  egg 
is  not  comparable  to  death  from  old  age  in  organisms  in  general, 
but  is  the  result  of  the  pecuHar  physiological  condition  of  the  egg 
almost  on  the  boundary  line  between  parthenogenesis  and  zygo- 
genesis.  The  conclusions  concerning  natural  death  which  Loeb 
has  drawn  from  the  behavior  of  this  egg  are  certainly  not  applicable 
to  death  from  old  age  (see  pp.  307-9).  A  few  other  eggs  show 
somewhat  similar  behavior,  but  in  all  of  them  a  more  or  less  similar 
physiological  condition  exists  and  their  behavior  cannot  be  made  the 
basis  for  conclusions  as  to  the  nature  of  death  in  general. 

In  experiments  of  my  own  the  susceptibihty  of  various  animal 
eggs  to  cyanide  before  and  after  fertihzation  has  been  tested,  both 
by  observing  the  occurrence  of  the  death  changes  and  by  determin- 
ing the  limits  of  recovery  in  a  given  concentration.  The  sea-urchin 
egg  and  the  eggs  of  Nereis,  Chaeto pterus ,  and  Hydroides,  among  the 
annelids,  are  all  somewhat  more  susceptible  to  cyanide  after  ferti- 
lization than  before,  although  the  difference  is  not  very  great.  In 
the  starfish  egg,  however,  the  susceptibihty  increases  markedly  in 
unfertiHzed  eggs  when  maturation  begins,  and  there  is  little  or 
no  further  change  on  fertihzation.  Since  increased  susceptibility 
means  increase  in  rate  of  metabolism,  these  results  agree  in  general 
with  those  obtained  by  other  methods,  although  the  increase  in 
susceptibility  to  cyanide  is  not  as  great  as  might  be  expected  if  the 
rate  of  oxidation  increases  from  three  to  six  times  with  fertilization. 
The  results  with  the  starfish  egg  indicate,  as  Loeb  suggested,  that 
here  the  chief  increase  in  rate  of  oxidation  occurs  with  maturation. 

PARTHENOGENESIS 

The  naturally  parthenogenic  egg  is  evidently  a  cell  which  pos- 
sesses the  capacity  to  react  to  its  physiological  or  physical  isolation 
from  the  parent  body  or  from  the  former  source  of  nutrition  or 
to  the  change  of  conditions  associated  with  its  extrusion  from  the 
body  by  the  initiation  of  a  normal  development.  Although  oxygen 
consumption  and  susceptibihty  of  parthenogenic  eggs  before  and 
after  isolation  have  not  been  determined,  the  observations  on  the 
starfish  egg  which  is  on  the  verge  of  parthenogenesis  and  the  very 


REJUVENESCENCE  IN  EMBRYO  AND  LARVA  407 

evident  increase  in  activity  in  parthenogenic  eggs  during  and  after 
maturation  leave  no  room  for  doubt  that  the  physiological  changes 
which  occur  in  zygogenic  eggs  after  the  entrance  of  the  sperm  occur 
in  parthenogenic  eggs  independently  of  the  sperm.  Moreover, 
among  animals  most  parthenogenic  eggs  undergo  only  one  matura- 
tion division  before  beginning  development.  It  was  also  pointed 
out  in  chap,  xiii  that  in  many  cases  parthenogenic  eggs  are  appar- 
ently less  highly  differentiated  morphologically,  and  younger  phys- 
iologically, than  zygogenic  eggs  of  the  same  species. 

The  obvious  conclusion  in  the  light  of  the  various  facts  is  that 
eggs  which  are  capable  of  parthenogenic  development  in  nature  are 
less  highly  specialized  as  gametic  cells  than  those  which  require 
fertihzation.  They  react  to  isolation  by  undergoing  dedift'crentia- 
tion  and  reconstitution  into  new  individuals,  and  in  this  respect 
they  resemble  the  pieces  from  the  bodies  of  many  lower  animals, 
such  as  Planaria,  which  undergo  reconstitution  when  isolated. 
The  capacity  of  parts  of  the  body  for  reacting  to  physiological 
or  physical  isolation  by  dedifferentiation  varies  inversely  as  the 
degree  of  physiological  stability  of  the  structural  substratum  (see 
pp.  39-42).  But  physiological  stability  of  the  substratum  appar- 
ently increases  during  individual  development  and  also  during  the 
course  of  evolution,  and  often  varies  to  a  considerable  extent  in 
related  species.  Since  the  development  of  the  primitive  egg  cell 
into  an  egg  is  apparently  subject  to  the  same  laws  as  the  develop- 
ment of  other  parts  of  the  body,  the  parthenogenic  egg  must  repre- 
sent an  earlier  stage  of  development  than  the  zygogenic  egg  of  the 
same  species.  But  it  does  not  by  any  means  follow  that  the  eggs 
of  all  species  would  develop  parthenogenically  if  they  were  iso- 
lated at  a  sufficiently  early  stage.  Since  the  bodies  of  different 
species  and  the  different  tissues  of  the  same  individual  possess  very 
different  degrees  of  reconstitutional  capacity,  we  must  e.xpect  to 
find  differences  of  the  same  sort  in  eggs.  Moreover,  since  the 
formation  of  gametes  is  characteristic  of  relatively  late  stages  in 
the  individual  Hfe  history,  we  should  expect  a  rather  high  degree 
of  physiological  stability  in  the  eggs  of  most  species  and  partheno- 
genesis in  comparatively  few.  As  a  matter  of  fact,  parthenogenesis 
occurs  only  here  and  there  among  organisms,  but  it  is  of  interest  to 


4o8  SENESCENCE  AND  REJUVENESCENCE 

note  that  it  is  relatively  frequent  in  the  lower  plant  s,  the  algae  and 
fungi.  To  what  extent  it  may  occur  among  the  lower  animals  is 
not  fully  known,  though  apparently  it  appears  c  hiefly  as  a  charac- 
teristic of  certain  groups  without  relation  to  their  systematic  posi- 
tion. Finally,  we  cannot  expect  to  find  parthenogenesis  ne  cessarily 
associated  with  a  high  degree  of  reconstitutional  capa  city  in  other 
parts  of  the  body,  for  the  physiological  condition  of  the  primitive 
germ  cells  from  which  eggs  are  formed,  the  rate  of  gr  owth  of  the 
egg,  the  character  and  amount  of  its  nutrition,  and  doubtless  many 
other  factors,  must  be  concerned  in  determining  whether  it  shall  be 
parthenogenic  or  zygogenic. 

From  this  point  of  view  the  parthenogenic  egg  is  a  cell  which 
has  undergone  more  or  less  development  as  a  gamete  but  still  re- 
tains the  capacity  to  initiate  dedifferentiation  and  re  constitution 
independently  of  union  with  a  male  gamete.  In  this  respect  it 
resembles  the  less  highly  specialized  cells  of  other  tissues  rather 
than  the  gametes. 

Much  evidence  has  accumulated  to  show  that  in  the  higher  seed 
plants  reproduction  of  a  new  sporophyte  generation  very  often 
occurs  in  various  other  ways  than  by  the  fertilization  of  a  zygogenic 
egg.  In  some  cases  the  reproductive  cell  is  not  the  egg  cell,  but  a 
vegetative  cell  of  the  gametophyte  and  the  reproductive  process  is 
known  as  apogamy;  in  other  cases  the  maturation  divisions  char- 
acteristic of  spore  formation  do  not  occur,  i.e.,  there  is  apospory, 
but  a  gametophyte  containing  a  parthenogenic  egg  is  formed;  in 
still  other  cases  the  reproductive  cell  is  not  even  a  part  of  the 
gametophyte,  but  a  cell  of  the  nucellus  which  corresponds  to  the 
sporangium.  There  can  be  little  doubt  that  in  such  cases  the 
reproductive  cell  does  not  attain  the  specialized  condition  and 
advanced  age  characteristic  of  the  zygogenic  egg.  The  final  stages 
of  progressive  development  are  omitted  in  one  generation  or  the 
other. 

THE  EXPERIMENTAL  INITIATION  OF  DEVELOPMENT 

Through  the  extensive  investigations  of  Loeb,  Delage,  Bataillon, 
aild  many  others  during  the  last  twenty  years  it  has  been  demon- 
strated that  the  eggs  of  various  species  of  animals  which  in  nature 


REJUVENESCENCE  IN  EMBRYO  AND  LARVA  409 

require  fertilization  for  their  development  can  be  induced  experi- 
mentally to  develop  without  fertilization.  General  agreement  has 
not  yet  been  reached  as  to  the  nature  of  the  changes  concerned  in 
the  initiation  of  development,  but  there  can  be  no  doubt  that  the 
increased  metabolic  activity  which  in  nature  follows  fertilization 
may  be  brought  about  by  the  action  of  certain  experimental  con- 
ditions. A  great  variety  of  agents  and  conditions  have  been  em- 
ployed in  these  experiments.  Harvey  ('10)  has  tabulated  the 
different  methods.  A  few  of  these  methods  bring  about  in  certain 
species  a  normal,  orderly  development  like  that  which  occurs  after 
fertilization.  With  many  of  the  so-called  parthenogenic  agents, 
however,  and  in  some  species  with  all,  the  changes  which  are  initi- 
ated differ  more  or  less  widely  from  normal  development.  In  some 
cases  development  may  proceed  more  or  less  normally  through 
the  earlier  stages,  but  ends  in  death  at  or  before  a  certain  stage; 
in  others  the  forms  produced  are  clearly  abnormal  from  the  begin- 
ning; in  still  others  only  a  few  divisions,  or  only  changes  in  the 
membrane,  occur  before  death.  In  certain  cases  also  some  degree 
of  differentiation  without  any  cell  division  results  from  the  use  of 
these  agents. 

All  of  these  experimental  effects  have  very  commonly  been 
regarded  as  initiation  of  development,  but  if  the  term  ''develop- 
ment" means  anything,  it  means  an  orderly  series  of  events  leading 
to  a  certain  definite  result.  The  course  of  events  and  the  result 
attained  are  subject  to  more  or  less  variation,  and  it  is  not  always 
possible  to  make  a  sharp  distinction  between  what  is  and  what  is 
not  development.  Nevertheless,  it  is  evident  that  many  of  these 
experimental  treatments  of  the  egg  do  not  initiate  development, 
but  a  change  which  lacks  some  of  the  essential  features  of  develop- 
ment and  soon  leads  to  death.  To  maintain  that  any  experimental 
agent  or  condition  which  brings  about  some  degree  or  kind  of 
cellular  activity  in  the  egg  initiates  development  is  to  lose  sight 
entirely  of  the  fundamental  characteristics  of  development;  and  to 
use  such  experimental  data  indiscriminately  as  a  basis  for  con- 
clusions concerning  the  nature  of  fertilization  is  certainly  not  a 
justifiable  procedure.  It  cannot  be  doubted,  however,  that  devel- 
opment in  the  strictest  sense  is  initiated  experimentally  in  certain 


4IO  SENESCENCE  AND  REJUVENESCENCE 

cases  and  by  certain  methods,  and  no  criticism  can  detract  from 
the  importance  and  interest  of  this  fact. 

The  questions  which  have  been  most  widely  discussed  in  con- 
nection with  this  held  of  investigation,  viz.,  the  nature  of  the 
changes  produced  in  the  egg  and  the  manner  in  which  the  experi- 
mental conditions  act  to  produce  them,  are  outside  the  range  of 
the  present  discussion.  The  point  to  which  I  desire  particularly 
to  call  attention  is  the  difference  in  the  reaction  of  the  eggs  of 
different  animals  to  the  experimental  conditions.  Some  eggs  react 
readily  to  a  variety  of  experimental  conditions  and  give  loo  per 
cent,  or  nearly,  of  normal  embryos  or  larvae,  while  others,  even  in 
the  most  favorable  cases,  give  only  a  small  percentage  of  normal 
forms,  or  react  only  to  certain  experimental  conditions,  and  still 
others  are  refractory  to  all  methods  and  have  never  been  known 
to  develop  except  when  fertiUzed.  In  the  egg  of  the  starfish,  for 
example,  which  is  on  the  verge  of  natural  parthenogenesis,  develop- 
ment can  apparently  be  initiated  by  almost  any  shght  stimulus, 
while  the  egg  of  the  sea-urchin  is  somewhat  less  susceptible  to  the 
various  agents  and  conditions  employed  to  initiate  development, 
and  many  other  eggs  are  only  sKghtly  or  not  at  all  susceptible. 
Our  knowledge  along  this  line  is  as  yet  somewhat  fragmentary,  for, 
although  changes  of  some  kind  and  degree  have  been  experimentally 
induced  in  the  eggs  of  many  different  species  of  invertebrates  and  a 
few  vertebrates,  no  systematic  comparative  study  along  these  lines 
has  yet  been  attempted.  But  that  great  differences  in  the  capacity 
to  begin  development  without  fertiUzation  exist  in  different  eggs 
is  a  demonstrated  fact,  and  the  probabihty  that  these  differences 
are  associated  with  the  different  degrees  of  speciahzation  and  differ- 
entiation of  eggs  at  once  suggests  itself.  If  the  eggs  of  different 
species  represent  various  degrees  of  speciahzation,  all  gradations 
from  natural  parthenogenesis  through  the  various  degrees  of  sus- 
ceptibility to  experimental  parthenogenic  agents  to  the  strictly 
zygogenic  condition,  in  which  the  egg  reacts  only  to  the  entrance 
of  the  sperm,  must  be  expected  to  occur.  Apparently  some  eggs 
can  be  aroused  from  their  quiescent  condition  and  started  along  the 
course  of  development  in  a  great  variety  of  ways,  some  of  which  may 
differ  widely  from  the  process  of  fertilization,  while  others  can  be 


REJUVENESCENCE  IN  EMBRYO  AND  LAR\A  411 

aroused  only  by  experimental  conditions  which  approximate  more 
closely  the  conditions  of  fertilization,  and  still  others  only  by 
fertilization  itself,  or  conditions  essentially  identical  with  it.  More- 
over, it  is  by  no  means  certain  that  the  conditions  concerned  in 
fertilization  are  exactly  the  same  in  all  cases.  The  morphological 
dilTerences  in  the  gametes  of  different  species  show  clearly  enough 
that  the  course  of  gametic  development  is  not  always  the  same, 
and  the  assumption  that  the  action  of  the  sperm  is  always  the  same 
seems  to  be  unjustified.  The  result  is,  of  course,  essentially  similar 
in  all  cases,  i.e.,  increased  metabolic  activity,  transformation  of 
nutritive  substances,  and  cell  division,  but  different  factors  or 
combinations  of  factors  may  be  concerned  in  producing  it  in  differ- 
ent cases.  The  differences  in  the  reaction  of  different  eggs  to  the 
experimental  parthenogenic  agents  suggest  that  various  degrees  of 
specialization  exist  in  the  process  of  fertihzation  itself.  The  con- 
ception of  the  gametes  as  highly  speciaHzed,  physiologically  old 
cells  places  the  whole  problem  of  the  initiation  of  development  by 
either  experimental  or  natural  means  in  a  new  light. 

OXYGEN   CONSUMPTION   AND   HEAT   PRODUCTION   DURING   EARLY 

STAGES   OF   DEVELOPMENT 

The  first  stage  of  development  is  a  period  of  repeated  cell 
division,  the  cleavage  period,  during  which  the  proportion  of 
active  cytoplasm  and  nuclear  substance  increases  at  the  expense 
of  substances  which  were  accumulated  in  the  egg  during  its  growth 
and  have  been  previously  inactive;  or  in  some  organisms,  where 
the  egg  itself  contains  but  little  nutritive  material,  it  becomes 
dependent  at  an  early  stage  on  nutriment  from  without. 

Authorities  are  generally  agreed  that  during  at  least  some  part 
of  this  period  an  acceleration  in  the  rate  of  metabolism  occurs.' 
According  to  Warburg  and  Loeb  and  Wasteneys  the  ox>'gen  con- 
sumption of  sea-urchin  eggs  increases  during  the  course  of  cleavage. 
In  the  egg  of  the  mollusk  Aplysia  limacina  Buglia  found  that  the 
oxygen  consumption  decreased  slightly  while  carbon-dioxide  pro- 
duction remained  uniform  during  the  earhest  stages  of  cleavage, 
but  in  later  embryonic  stages  both  underwent  a  marked  increase 

'  Buglia, 'oS;   Loeb  and  Wasteneys, '11;   Meyerhof, '11;   Warburg, 'oS, '10. 


412  SENESCENCE  AND  REJUVENESCENCE 

and  finally  became  nearly  uniform  again  in  early  larval  stages. 
Meyerhof  has  shown  that  the  heat  production  of  the  sea-urchin 
egg  increases  steadily  up  to  the  larval  stage;  at  the  sixty-four-cell 
stage  it  is  about  twice  as  great  as  during  the  first  hour  after  fertili- 
zation; when  the  larva  begins  to  swim  it  is  three  times  as  great, 
and  at  a  stage  four  hours  later,  four  times  as  great.  Heat  produc- 
tion in  the  Aplysia  embryo  decreases  during  the  first  few  cleavages, 
then  increases  rapidly  to  the  larval  stage,  when  it  becomes  nearly 
uniform,  i.e.,  the  changes  in  heat  production  in  Aplysia  are  essen- 
tially parallel  to  the  changes  in  oxygen  consumption  and  carbon- 
dioxide  production  as  determined  by  Buglia. 

All  of  these  data  indicate  that  at  least  the  oxidation  processes 
increase  in  rate  during  the  earlier  stages  of  development,  and  the 
general  behavior  of  the  developing  embryo,  the  increase  in  the 
amount  of  metabolically  active  cytoplasm  and  nuclear  substance, 
and  the  decrease  in  amount  of  yolk  where  yolk  is  present  suggest 
that  not  merely  oxidation  but  metabolic  activity  in  general 
undergoes  a  marked  increase  during  this  period.  In  short,  this  is  a 
period  of  physiological  rejuvenescence. 

CHANGES    IN   SUSCEPTIBILITY   DURING   EARLY   STAGES 

Lyon  ('02)  found  that  the  susceptibiHty  to  cyanide  of  the  sea- 
urchin  egg  underwent  a  gradual  increase  during  the  course  of 
cleavage,  and  I  have  determined  the  susceptibility  to  cyanide  dur- 
ing early  development  in  a  number  of  animal  species.  In  these 
experiments  the  susceptibility  was  measured  in  most  cases  by  the 
limits  of  recovery,  that  is,  the  length  of  time  in  the  cyanide  solu- 
tion at  which  recovery  ceased  to  occur  on  return  to  water.  It  was 
also  possible  in  most  cases  to  determine  the  survival  time  by 
observing  the  death  changes  in  the  cyanide.  A  part  of  the  results 
of  these  experiments  appear  in  the  following  tables.  For  the  sake 
of  simphcity  only  the  average  survival  times  are  given,  viz.,  the 
average  length  of  time  in  cyanide  necessary  to  prevent  any  visible 
degree  of  recovery  after  return  to  sea-water.  These  tables  serve 
merely  to  give  a  general  idea  of  the  changes  in  susceptibility  and 
do  not  show  the  differences  or  the  different  rates  of  change  in  the 
susceptibility  of  dift'erent  regions  of  the  embryos. 


REJUVENESCENXE  L\  EMBRYO  AXI)  LAR\A  413 

In  both  starfish  and  sea-urchin  the  susceptibility  increases  very 
greatly,  and  more  in  the  starfish  than  in  the  sea-urchin,  up  to  the 
early  gastrula  stage  and  then  begins  to  decrease  slightly  as  the 
larval  structure  begins  to  develop.  At  this  stage  the  cells  have 
lost  the  differentiation  of  the  egg,  the  chemically  active  protoplasm 
has  undergone  great  increase  at  the  expense  of  the  inactive  substance 
and  has  attained  the  maximum,  and  from  this  stage  on  the  develop- 
ing organism  begins  to  grow  old. 

TABLE  VIII 

Starfish  {Asterias  forbesii) 
KCX  o.oi  mol. 

Stage  of  Average  Survival  Time 

Development  in  Hours  and  Minutes 

Unfertilized  egg  undergoing  maturation 11.30 

30  minutes  after  fertilization 11  ■  30 

2-8  cells 10 .  30 

64-128  cells 5 .  30 

Blastulae  before  movement 1.15 

Early  gastrulae 1.35 

Advanced  gastrulae i .  20 

Young  bipinnaria  larva 3 .  00 

TABLE  IX 

Sea-Urchin  {Arbacia  pimctulata) 
KCN  0.005  iTiol. 

Stage  of  Average  Survival  Time 

Development  in  Hours  and  Minutes 

Unfertilized  egg 8.15 

20  minutes  after  fertilization 6. 45 

4-8  cells 5 .  45 

Late  cleavage 3  •  30 

Early  gastrulae 2.15 

Advanced  gastrulae 3 .  00 

Prepluteus 3  •  30 

In  this  connection  it  is  of  great  interest  to  note  that  in  the  starfish 
and  sea-urchin  and  various  other  species  the  late  blastula  and  early 
gastrula  stages  appear  to  be  critical  stages  in  development  under 
many  experimental  conditions,  e.g.,  in  experimental  partheno- 
genesis, in  many  hybrids  and  under  the  action  of  various  external 
agents.     Development  may  proceed  with  little  or  no  disturbance 


414  SENESCENCE  AND  REJUVENESCENCE 

up  to  these  stages  and  then  stops  or  becomes  abnormal.  If  these 
stages  are  passed  successfully,  further  development  is  likely  to 
follow  its  usual  course.  It  is  easy  to  see  why,  if  anything  is  wrong, 
it  should  become  evident  during  these  stages,  for  they  represent 
the  period  when  the  intrinsic  metabolic  activity  of  the  cells  is  greater 
than  at  any  other  period  of  the  life  history,  and  the  physical  condi- 
tion of  the  protoplasm  which  is  of  course  correlated  with  the  high 
rate  of  metabohsm  must  likewise  be  most  susceptible  to  change  at 
this  time.  Internal  or  external  factors,  which  produce  little  or 
no  efTect  when  the  metaboHc  and  protoplasmic  susceptibility  is 
lower,  may  at  this  time  bring  about  changes  which  either  lead  to 
death  or  profoundly  modify  the  further  course  of  development. 

The  different  behavior  of  the  two  eggs  in  relation  to  fertilization 
which  was  mentioned  in  an  earlier  section  (pp.  405-6)  appears  in 
the  tables.  The  starfish  egg  shows  scarcely  any  increase  in  sus- 
ceptibility just  after  fertihzation,  while  in  the  sea-urchin  egg  the 
increase  is  marked. 

TABLE  X 

Nereis  limhata 
KCN  0.005  rnol- 

Stage  of  Average  Survival  Time 

Development  in  Hours  and  Minutes 

2-4  cells 13.45 

Early  gastrulae 11.30 

Early  larvae  hatching 7 .  30 

Larvae  8  hours  after  hatching 3  •  30 

Larvae  with  two  pairs  of  setae 45 

Full-grown  larvae i .  40 

Advanced  larvae 2 .  30 

In  Nereis,  an  annehd  worm,  the  susceptibility  increases  up  to  the 
larval  period  and  during  this  period  begins  to  decrease.  Undoubt- 
edly the  great  increase  in  susceptibility  in  the  early  larval  stages  is 
due  in  part  to  the  appearance  and  increase  of  motor  activity  and 
functional  stimulation.  The  larva  is  a  highly  organized  animal 
with  sense-organs  and  muscles,  and  its  rate  of  metabolism  is  higher 
than  that  determined  by  conditions  existing  within  its  cells  because 
it  reacts  to  external  stimuli.  But  even  during  the  larval  period 
very  considerable  changes  in  susceptibihty  occur  which  must  belong 


REJUVEXESCEXCE  IX  EMBRYO  AXI)  LARVA  415 

to  the  age  cycle.     In  the  earlier  larval  stages  the  animal  is  still 
growing  young,  while  in  the  later  stages  it  is  growing  old. 

Between  Nereis  and  another  anneUd,  Arenicola  cristata,  an 
interesting  difference  exists.  During  the  period  of  rejuvenescence 
the  Nereis  embryo  obtains  its  nutritive  material  from  the  yolk  in 
the  egg,  but  this  material  is  used  up  before  the  end  of  the  lars-al 
period,  and  metamorphosis  from  the  larval  to  the  adult  form  does 
not  occur  unless  the  larva  can  obtain  food  from  without.  The 
egg  of  Arenicola,  however,  contains  sufficient  yolk  to  carry 
development  completely  through  the  larval  period  and  meta- 
morphosis to  the  stage  of  a  worm  with  five  or  six  segments,  after 
which  food  from  without  is  necessary.  In  both  these  forms  the 
embryonic  period  of  increase  in  susceptibility,  i.e.,  of  rejuvenescence, 
ends  at  about  the  stage  when  the  last  of  the  yolk  is  used  up:  the 
Nereis  embryo  continues  to  grow  younger  only  up  to  the  larval 
stage,  while  rejuvenescence  in  Arenicola  continues  through  the 
larval  stage,  the  metamorphosis,  and  up  to  the  six-segment  stage 
of  the  worm.  During  this  period  yolk  is  being  transformed  into 
chemically  active  nuclear  substance  and  cytoplasm,  and  the  pro- 
portion of  chemically  active  to  inactive  substance  increases  to  a 
certain  point  where  the  accumulation  of  new  structural  substance, 
together  with  any  part  of  the  old  that  may  remain,  balances  the 
synthesis  of  active  protoplasm. 

Susceptibility  determinations  have  been  made  for  only  two  other 
species  of  annelids,  Chaetopterus  pergametitaceics  and  Ilydroides 
dianthus,  and  in  both  rejuvenescence  takes  place  during  the  embr}-- 
onic  period,  as  in  Nereis,  but  the  stage  at  which  rejuvenescence 
gives  place  to  senescence  was  not  determined  in  these  forms. 

Among  the  vertebrates  the  eggs  of  two  species  of  fish  have  been 
used  for  susceptibiHty  determinations.  In  contrast  to  the  holo- 
blastic  egg  of  the  starfish,  sea-urchin,  and  annelid  in  which  the 
yolk  is  in  all  or  some  of  the  cells  and  the  whole  egg  divides,  the  fish 
eggs  are  meroblastic,  most  of  the  yolk  being  separated  from  the 
active  protoplasmic  part  of  the  egg,  and  only  the  latter  divides. 
In  such  eggs  the  embryo  begins  at  a  rather  early  stage  to  feed  on 
the  yolk  outside  its  own  cells,  and  its  relation  to  the  nutritive  supply 
becomes  similar  to  that  of  the  animal  developing  from  a  holoblastic 


4i6 


SENESCENCE  AND  REJUVENESCENCE 


egg  which  has  used  up  all  its  yolk.  It  is  a  point  of  some  interest 
to  determine  at  what  stage  the  embryonic  period  of  rejuvenescence 
ends  in  such  cases.  The  survival  times  for  these  two  forms  are 
given  in  Tables  XI  and  XII. 

TABLE  XI 

Fundulus  heteroclitus 
Saturated  Phenyl  Urethane  in  Sea-Water 


Stage  of  Development 

Length  of  Time  after 

Fertilization  in 
Hours  and  Minutes 

Average  Survival 

Time  in  Hours  and 

Minutes 

2  cells             

3-3° 
24 

45 
69 

117 
408 

11-45 

Advanced  oeriblast 

4.30 

Embrj'o  just  appearing 

Embrj'o  with  3-4  somites. .  .  . 
Embryo  with  heart  beating .  . 
At  time  of  hatching 

5-30 
6.00 

7-3° 
2.00 

TABLE  XII 

Tautogolahrus  adspcrsus 
KCN  0.005  mol. 


Stage  of  Development 

Length  of  Time  after 

Fertilization  in 
Hours  and  Minutes 

Average  Survival 

Time  in  Hours  and 

Minutes 

1 5  minutes  after  fertilization 
1—2  cells 

015 
0.50 
2 

5 

7 
20 

42 

5  5-60 

10.45 
10.10 

4-8  cells          

7.30 

Many  cells 

6.3s 

Periblast 

5-45 

Embryo  just  appearing 

Heart  beatine        

0-45 
015 

Newly  hatched 

0.20 

Phenyl  urethane  was  used  instead  of  cyanide  in  determining  the 
susceptibility  of  the  Fundulus  egg,  because  the  membrane  of  this 
egg  is  impermeable  to  cyanide,  as  it  is  to  many  other  substances,  so 
that  even  in  high  concentrations  development  is  not  retarded,  while 
for  phenyl  urethane  the  permeability  is  practically  complete. 

Rejuvenescence  occurs  in  Fundulus  during  the  early  stages  of 
development,  as  indicated  by  the  increase  in  susceptibility,  but 
as  soon  as  the  embryo  begins  to  form,  it  gives  place  to  senescence. 
The  great  increase  in  susceptibiHty  between  establishment  of  the 


REJUVEXESCE.\XE  L\  EMBRYO  AND  LARVA  417 

heart-beat  and  hatching  is  probably  due  in  pari  to  increased  func- 
tional activity  and  stimulation,  but  it  may  be  largely  the  con- 
sequence of  the  increasing  lipoid  content  of  the  nervous  system  in 
connection  with  medullation  of  the  nerves,  a  change  which  would 
increase  the  relative  concentration  of  phenyl  urethane  in  the 
nervous  system  and  so  might  intensify  its  action  (see  pp.  75-76). 
In  the  vertebrates  particularly  these  changes  in  the  nervous  system 
make  the  use  of  the  susceptibihty  method  with  highly  fat-soluble 
substances  difficult  in  the  later  stages  of  development.  If  this 
second  increase  in  susceptibility  is  due  to  the  increase  of  fatty 
substances  in  the  nervous  system,  it  of  course  does  not  mean  that  a 
second  period  of  rejuvenescence  occurs,  but  rather  that  the  sus- 
ceptibility to  phenyl  urethane  is  not  a  measure  of  the  metabolic 
condition  at  this  stage.  In  all  probabiHty  senescence  and  decrease 
in  metabolic  rate  continue  from  the  stage  where  the  susceptibility 
first  begins  to  decrease. 

In  Tautogolabrus  the  period  of  increasing  susceptibility  con- 
tinues up  to  the  time  of  hatching,  and  almost  all  of  the  increase 
occurs  before  movement  or  special  function  of  organs  begins.  At 
the  periblast  stage,  where  Fundulus  shows  the  highest  suscepti- 
bility, Tautogolabrus  has  undergone  only  half  of  its  increase  and  the 
total  increase  of  susceptibihty  in  the  latter  is  about  twice  that 
in  the  former.  These  differences  between  the  two  forms  are 
undoubtedly  associated  with  differences  in  the  course  of  develop- 
ment. The  second  column  of  Tables  XI  and  XII  shows  that 
Tautogolabrus  develops  three  or  four  times  as  rapidly  as  Fundulus, 
and  its  development  up  to  the  time  of  hatching  occurs  very  largely 
at  the  expense  of  nutritive  material  in  the  protoplasmic  part  of  the 
egg,  but  little  of  the  separate  yolk  mass  being  used  during  this 
stage,  while  in  Fundulus  most  of  the  yolk  is  used  before  hatching. 
It  is  also  evident  that  the  protoplasms  of  the  two  species  differ 
widely  in  capacity  for  growth,  for  the  egg  of  Fundulus  is  very  much 
larger  and  the  adult  usually  much  smaller  than  that  of  Tautogola- 
brus. Apparently  the  differences  between  the  two  eggs  determine 
that  the  degree  of  rejuvenescence  is  much  greater  and  that  the 
period  of  rejuvenescence  extends  to  a  much  later  stage  of  develop- 
ment in  Tautogolabrus  than  in  Fundulus. 


4i8  SENESCENCE  AND  REJUVENESCENCE 

In  the  frog  and  salamander,  the  only  other  vertebrates  for  which 
embryonic  susceptibiHties  have  been  determined,  the  changes  are 
very  similar  to  those  described  for  other  forms.  From  the  time  of 
fertilization  on,  through  cleavage,  gastrulation,  and  the  formation 
of  the  embryo,  and  somewhat  beyond  the  stage  of  hatching,  the 
average  susceptibihty  increases.  As  in  the  fishes,  the  results  in  the 
later  stages  are  perhaps  comphcated  by  the  increased  metabolic 
activity  connected  with  the  functional  activity  of  special  organs 
and  with  movement,  or  by  changes  in  the  nervous  system,  but  as 
regards  the  earher  stages  this  is  certainly  not  the  case. 

All  of  these  data,  as  well  as  those  on  oxygen  consumption,  are 
in  full  agreement  with  the  observed  facts  of  development.  It  is 
well  known  that  as  cleavage  goes  on  the  rate  of  cell  division  is 
accelerated  and  other  developmental  changes  proceed  more  and 
more  rapidly  up  to  a  certain  stage.  In  general  the  rejuvenes- 
cence of  certain  parts  of  the  embryo,  and  particularly  of  the  apical 
region,  where  the  metaboUc  rate  is  originally  highest,  proceeds  more 
rapidly  than  that  of  other  parts  and  is  completed  earlier. 

THE   MORPHOLOGICAL    CHANGES    DURING   EARLY   DEVELOPMENT 

The  morphological  changes  during  the  period  of  increasing 
susceptibihty  consist  in  an  increase  of  nuclear  as  compared  with 
cytoplasmic  substance  and  in  the  decrease  and  disappearance  of 
the  yolk  in  the  cytoplasm  and  the  increase  of  the  amorphous, 
undifferentiated,  or  embryonic  cytoplasm;  often  also,  particularly 
in  the  later  stages,  the  new  morphological  features  connected  with 
the  new  process  of  dififerentiation  begin  to  appear.  The  increase, 
both  absolute  and  relative,  in  total  nuclear  volume  is  a  character- 
istic feature  of  embryonic  development  in  animals  and  is  evident 
from  observation.  It  has  often  been  stated  that  the  nuclear 
volume  or  nuclear  substance  increases  in  geometrical  progression 
during  this  period,  but  measurements,  so  far  as  they  have  been 
made,  indicate  that  this  is  by  no  means  always  the  case.  Godlewski 
('08)  has  found  that  in  the  sea-urchin  from  the  four-ceh  to  the 
sixty-four-cell  stage  the  nuclear  volume  does  increase  ahnost  in 
geometrical  progression,  while  from  the  sixty-four-cell  stage  on 
there  is  but  httle  further  increase.     During  the  period  of  nuclear 


REJUVENESCE^XE  IN  EMBRYO  AM)  LAR\  A  419 

increase  there  is  no  increase,  but  rather  a  decrease,  in  total  cyto- 
plasmic volume,  for  the  nuclear  substance  is  formed  at  the  expense 
of  the  cytoplasm  or  of  substances  contained  in  it;  consequently 
the  relative  increase  in  nuclear  substance  is  somewhat  greater  than 
the  absolute.  According  to  Erdmann  ('08),  the  nucleoplasmic 
relation,  that  is,  the  volume  of  the  nucleus  in  relation  to  the  volume 
of  the  cytoplasm,  undergoes  very  great  increase  from  the  four-cell 
stage  to  the  gastrula  in  the  sea-urchin,  and  the  volume  of  the 
chromosomes,  in  relation  both  to  cell  volume  and  to  nuclear  volume, 
also  increases  during  this  period.  Conklin  ('12),  in  a  study  of  the 
mollusk  Crepidula,  also  finds  an  increase  in  total  nuclear  volume 
during  cleavage,  though  by  no  means  so  great  as  that  found  in  the 
sea-urchin. 

The  change  in  the  nucleoplasmic  relation  during  this  period  is 
evidently  in  the  reverse  direction  from  that  which  it  underwent 
during  the  growth  period  of  the  gametes.  Undoubtedly  the 
increase  in  relative  nuclear  volume  during  early  development  is,  as 
Conklin  points  out,  an  important  factor  in  the  acceleration  of  meta- 
boHc  activity,  but  it  is  not  the  only  nor  even  the  primary-  factor, 
for  the  acceleration  may  begin  before  the  nuclear  increase,  and 
under  other  conditions  acceleration  of  metabolism  may  occur  with- 
out such  increase.  The  increase  in  nuclear  volume  is  an  indication 
rather  than  a  cause  of  the  metaboHc  changes  which  the  embryo  is 
undergoing  during  this  period.  Moreover,  as  regards  the  sperma- 
tozoon, entrance  into  the  egg  constitutes  a  sudden  and  enormous 
increase  in  cytoplasmic  volume,  yet  the  spermatozoon  undergoes 
regressive  changes  as  well  as  the  egg.  The  general  significance  of 
the  nucleoplasmic  relation  for  the  problem  of  age  is  considered  in 
chap,  xvi  (see  also  pp.  284-86). 

In  most  animal  eggs  the  cytoplasm  contains  more  or  less  fatty 
substance — the  yolk — in  the  form  of  granules,  droplets,  or  large 
masses,  and  in  such  eggs  the  most  conspicuous  cytoplasmic  change 
during  the  early  stages  of  development  is  the  gradual  disaj^jjearance 
of  this  yolk.  But  even  in  eggs  which  contain  no  visible  yolk  the 
cytoplasm  becomes  more  homogeneous  in  appearance,  and  cyto- 
plasmic strands,  granules  of  various  sorts,  and  other  structural 
features  of  the  egg  disappear  wholly  or  in  part.     At  the  same  time 


420  SENESCENCE  AND  REJUVENESCENCE 

that  these  regressive  processes  are  going  on,  progressive  changes 
are  occurring  and  new  structural  features  are  beginning  to  appear. 
In  some  embryos  these  do  not  become  visible  or  conspicuous  until 
the  regressive  changes  are  far  advanced,  while  in  others,  such,  for 
example,  as  certain  anriehds  and  mollusks,  in  which  larval  forms 
differentiate  very  early  in  development,  they  may  begin  to  appear 
during  the  first  few  divisions  following  fertilization,  or  some  of  the 
structural  features  of  the  egg  may  be  carried  over  into  the  larva. 
In  short,  both  the  degree  and  rate  of  morphological  regression,  as 
well  as  the  degree  and  rate  of  rejuvenescence  during  early  stages, 
vary  greatly  in  different  forms. 

LARVAL  STAGES  AND  METAMORPHOSIS 

In  many  animals  the  form  hatching  from  the  egg  is  widely 
different,  both  in  structure  and  in  behavior,  from  the  adult,  and  is 
known  as  a  larva:  sooner  or  later  this  form  undergoes  either  a 
gradual  or  a  somewhat  abrupt  transformation  or  metamorphosis 
into  the  adult  form.  The  question  as  to  the  nature  of  larval 
metamorphosis  and  the  internal  and  external  conditions  which 
determine  it  has  been  much  discussed,  and  various  hypotheses 
have  been  advanced.  Here,  however,  the  purpose  is  only  to  present 
a  few  suggestions  rather  than  to  attempt  extended  discussion. 

In  the  first  place  the  term  "larva"  is  a  loose  biological  term  with 
little  physiological  significance.  The  larva  is  merely  a  form  differ- 
ent from  the  adult  and  appearing  before  it  in  the  life  history.  But 
the  larva  of  an  annelid  which  develops  during  the  first  few  cell 
divisions  after  fertihzation  is  very  dift'erent  from  the  larva  of  an 
insect  or  a  frog  which  appears  only  after  thousands  of  divisions  and 
extensive  dift'erentiation.  The  larval  form  may  represent  an 
earlier  or  a  later  stage  in  the  developmental  history. 

In  many  invertebrates,  e.g.,  in  the  annelid  Nereis,  the  larval 
form  develops  during  the  period  of  rejuvenescence.  So  far  as  I 
have  been  able  to  deterpiine,  the  eggs  or  embryos  of  all  species 
in  which  the  larval  form  arises  very  early  possess  a  strongly  marked 
axial  gradient  and  individuation  progresses  rapidly,  while  in  those 
where  the  larval  period  occurs  at  a  later  stage  the  gradient  is  much 
less  clearly  marked  in  early  stages  and  develops  only  gradually. 


REJU\'ENESCENCE  IN  EMBRYO  AND  LARVA 


421 


The  larval  form  of  the  annelids,  moUusks,  Crustacea,  and  some 
other  invertebrate  groups  represents  chiefly  the  head  and  anterior 
regions  of  the  body,  and  metamorphosis  consists,  not  only  in  changes 
in  the  parts  already  formed,  but  in  the  addition  of  new  segments 
from  a  growing  region  just  in  front  of  the  posterior  end.  The  fully 
developed  larva  of  the  anneHd  Nereis,  for  example,  consists  of  the 
head  and  the  first  three  segments,  as  indicated  in  Fig.  197,  and  during 
the  transfonnation  of  this  free-swimming  form  into  the  worm  new 
segments  are  added  successively  at  the  posterior  end.     In  this  and 


Fig.  197. — Trochophore  larva  of  Nereis.    After  E.  B.  Wilson,  '92 

in  other  related  species  the  axial  gradient,  which  is  so  clearly  marked 
during  prelarval  stages,  becomes  less  and  less  distinct  in  the  larva, 
until,  as  metamorphosis  approaches,  the  growing  region  at  the 
posterior  end  shows  the  highest  metabolic  rate  of  any  part  of  the 
body.  These  changes  enable  us  to  gain  some  insight  into  the 
process  of  formation  of  new  segments.  The  head-region  under- 
goes rejuvenescence  and  begins  senescence  before  other  parts,  so 
that  in  the  larval  stage  its  metabolic  rate  begins  to  decrease  before 
that  of  the  more  posterior  regions.     But  even  before  its  metabolic 


42  2  SENESCENCE  AND  REJUVENESCENCE 

rate  begins  to  decrease,  the  rate  in  more  posterior  regions  is  in- 
creasing more  rapidly  than  in  the  head,  and  the  result  is  a  partial 
physiological  isolation  of  the  posterior  region  and  the  formation 
of  a  new  segment.  Similarly,  physiological  isolation  of  the  pos- 
terior region  from  the  first  segment  results  in  the  formation  of  the 
second,  and  isolation  from  the  second  in  the  formation  of  the 
third.  But  by  this  time  the  rate  of  metabolism  in  the  head-region 
is  decreasing,  and  a  Uttle  later  it  begins  to  decrease  in  the  first, 
then  in  the  second  and  the  third  segments.  Sooner  or  later  this 
process  leads  to  partial  physiological  isolation  of  the  posterior  end 
and,  if  food  is  present  to  provide  energy  and  substance  for  growth, 
another  segment  is  added  posteriorly,  and  so  on. 

In  the  Crustacea  the  process  is  essentially  similar.  In  the  lower 
Crustacea  the  earhest  larval  stage  represents,  as  in  Nereis,  the  head, 
and  three  segments  with  their  appendages,  and  new  segments  are 
added  successively  at  the  posterior  end.  Fig.  198  shows  a  stage  in 
the  metamorphosis  of  the  fairy  shrimp  Branchipus.  The  original 
larval  form  in  this  case  consisted  of  the  head  and  the  first  three 
segments  to  which  the  three  pairs  of  large  appendages  are  attached 
in  the  figure,  and  to  this  new  segments  are  successively  added  at 
the  posterior  end.  The  figure  shows  a  stage  in  which  a  large 
number  of  segments  have  already  formed,  but  are  not  yet  fully 
developed. 

In  the  insects  and  vertebrates  the  formation  of  the  segments 
occurs  before  hatching,  but  is  in  all  probabiHty  a  similar  process. 
The  changes  called  metamorphosis  in  the  insects  belong  to  a  much 
later  stage  of  development.  Here  the  larval  form,  which  has  fed 
and  grown  for  a  time  and  has  acquired  a  large  nutritive  reserve, 
undergoes  transformation  into  the  mature  form,  the  imago,  during 
the  pupal  stage  which  usually  shows  little  or  no  movement  and  does 
not  feed.  In  this  case  the  changes  seem  to  be  the  result  of  aging 
of  certain  of  the  larval  organs  in  consequence  of  which  growth  and 
development  of  certain  parts  previously  inhibited  now  becomes 
possible.  In  some  insects  many  of  the  larval  organs  actually  die 
and  undergo  complete  resorption  or  degeneration.  In  some  other 
invertebrates  parts  of  the  larva  die  and  are  cast  oH  bodily  when 
metamorphosis  begins. 


REJUVENESCENCE  IN  EMBRYO  AND  LAR\A 


423 


Apparently  in  all  ihese  cases  metamoqihosis  is  a  partial  physio- 
logical disintegration  of  the  individual  resulting  from  changes  in 
the  axial  gradient  during  the  earlier  stages  of  development,  or  from 
the  aging  and  death  of  certain  larval  organs.     Where  the  larval 


Fig.  198. — Larval  metamorphosis  of  Branchipus  (fairy  shrimp) 


period  occurs  at  a  very  early  stage  of  development  a  well-marked 
axial  gradient  and  a  relatively  high  tlegree  of  individuation  are 
present  at  the  beginning,  or  at  a  very  early  stage,  of  embryonic 
development. 


424  SENESCENCE  AND  REJUVENESCENCE 

Metamorphosis  in  the  amphibia  is  evidently  a  process  associated 
with  progressive  development  and  physiological  senescence,  and  it 
may  be  hastened  or  delayed  by  external  factors  which  accelerate  or 
retard  development;  but  the  physiological  factors  immediately 
concerned  in  bringing  about  the  changes  which  occur  are  still 
obscure.  Metamorphosis  unquestionably  results  in  a  higher  degree 
of  physiological  integration,  particularly  in  the  higher  amphibia, 
the  frogs  and  toads;  in  fact,  it  is  in  a  sense  a  new  integration 
within  the  previously  existing  individual.  In  the  substitution  of 
physiologically  younger  for  older  organs  and  parts,  which  apparently 
occurs  in  amphibian  metamorphosis,  differences  in  metabolic  rate 
may  play  a  part,  but  our  knowledge  is  at  present  too  incomplete 
to  permit  definite  conclusions. 

EMBRYONIC   DE\TELOPMENT   IN   PLANTS 

In  most  plants  embryonic  development  takes  place  within 
special  organs  of  the  parent  plant,  and  the  embryonic  stages  are 
not  accessible  to  physiological  investigation  as  are  those  of  many 
animals.  Moreover,  the  plant  ovum  does  not  in  most  cases  accumu- 
late a  large  supply  of  nutritive  substance  within  its  own  body,  but 
is  nourished  by  other  cells.  Only  in  certain  algae  and  fungi,  where 
embryonic  development  occurs  apart  from  the  parent  body,  is 
there  any  considerable  accumulation  of  nutritive  material  in  the 
egg  itself. 

So  far  as  I  am  aware,  no  determinations  of  oxygen  consumption, 
carbon-dioxide  production,  or  susceptibility  have  been  made  upon 
the  embryonic  stages  of  plants,  but  observation  indicates  clearly 
enough  that  the  metabohc  changes  during  these  stages  are  not 
fundamentally  different  from  those  in  animals.  Fertilization  in  the 
plant,  as  in  the  animal,  initiates  an  increased  activity  in  the  pre- 
viously quiescent  ovum,  repeated  division  occurs  with  an  absolute 
and  relative  increase  of  nuclear  substance,  and,  where  nutritive 
substances  are  present  in  the  egg,  they  gradually  disappear.  As 
in  the  animal,  the  cells  resulting  from  the  successive  divisions 
become  more  or  less  completely  "embryonic"  or  undifferentiated 
in  appearance,  and  from  such  cells  the  new  plant  individual  arises. 
There  is,  in  short,  every  visible  indication  of  a  process  of  regression 


REJUVENESCENCE  IN  EMBRYO  AND  LARVA  425 

and  rejuvenescence  in  the  early  stages  of  plant  development.  The 
youngest  stage  physiologically  is  jirobably  earlier  in  some  and  later 
in  other  plants,  as  in  different  animals,  but,  as  j)ointed  out  in 
chap.  X,  certain  parts  in  most  plants  remain  physiologically  young 
for  a  long  time,  or  indefinitely,  and  well-marked  dilTerentiation 
and  senescence  are  confined  to  other  parts. 

THE   DEGREE   OF   REJUVENESCENCE   IN    GAMETIC   AND   AGAMIC 

REPRODUCTION 

In  gametic  reproduction  the  organism  begins  its  life  history  as 
a  single  cell  resulting  from  the  union  of  two  highly  specialized, 
old  cells,  and  the  earlier  part  of  this  history  is  a  period  of  dediffer- 
entiation,  cell  division,  and  rejuvenescence.  In  many  cases  of 
agamic  reproduction  also  the  life  history  begins  with  a  single  cell, 
but  in  many  others  the  reproductive  body  is  a  cell  mass  often  con- 
taining various  differentiated  organs.  Evidently  in  those  cases 
where  a  single  specialized  cell  is  the  starting-point,  the  degree  of 
reconstitutional  change  involved  in  the  formation  of  a  new  indi- 
vidual is  in  general  greater  than  where  the  individual  arises  from  a 
large  mass  of  cells,  for  in  the  latter  case  some  of  the  cells  or  organs 
are  incorporated  as  parts  of  the  new  individual  with  but  little 
change.  It  has  been  shown  in  chap,  v,  for  example,  that  in  Planaria 
the  degree  of  reconstitution  and  rejuvenescence  varies  inversely 
as  the  size  of  the  isolated  piece:  in  the  large  piece,  while  certain  cells 
may  become  embr}'onic,  these  rapidly  differentiate  and  grow  old 
and  the  total  rejuvenescence  is  slight,  while  in  the  smaller  piece  the 
cells  undergo  more  change  and  the  total  rejuvenescence  is  greater 
in  amount.  In  the  single  cell  which  gives  rise  to  a  new  individual 
the  changes  are  still  greater,  and  the  degree  of  rejuvenescence  of 
the  whole  must  also  be  greater,  because  the  reconstitutional  changes 
are  very  extensive  and  involve  the  cell  as  a  whole.  Moreover,  if 
it  is  true  that  the  gametes  are  more  highly  specialized  than  single 
cells  which  reproduce  agamically,  we  must  conclude  that  the  degree 
of  rejuvenescence  is  in  general  greater  in  gametic  than  in  any 
form  of  agamic  reproduction,  that  is,  in  multicellular  organisms. 

If,  however,  the  same  degree  of  rejuvenescence  occurs  in  suc- 
cessive agamic  generations,  even  though  it  is  much  less  than  thai 


426  SENESCENCE  AND  REJUVENESCENCE 

occurring  in  gametic  reproduction,  the  agamic  process  may  be 
repeated  indefinitely  without  race  senescence.  The  failure  of 
agamic  reproduction  after  a  larger  or  smaller  number  of  agamic 
generations  is  not  due  to  the  fact  that  there  is  less  rejuvenescence 
connected  with  it  than  with  the  gametic  reproduction,  but  rather 
to  the  fact  that  under  the  existing  conditions  senescence  in  each 
agamic  generation  is  not  entirely  compensated  by  rejuvenescence 
in  each  reproduction,  and  race  senescence  results.  In  such  cases 
of  course  a  substitution  of  gametic  for  agamic  reproduction  will 
rejuvenate  the  race  and  make  possible  a  new  series  of  agamic 
generations.  This  course  has  from  time  to  time  been  followed  with 
the  potato,  when  a  particular  race  has  seemed  to  show  signs  of 
decrease  in  vitality  or  commercial  value,  and  often  with  good  results. 
There  is,  however,  every  reason  to  believe  that  a  change  of  the 
right  kind  in  conditions  of  cultivation  would  accomplish  the  same 
result  without  breeding  from  the  seeds  instead  of  the  tubers. 
Doubtless  the  gametic  process  affords  a  less  difiicult  and  more 
rapid  method  of  accomplishing  the  desired  result,  but  it  is  probably 
not  the  only  method. 

In  many  organisms,  under  the  ordinary  conditions  of  nature, 
senescence  is  evidently  not  completely  compensated  by  the  reju- 
venescence occurring  in  agamic  reproduction,  and  progressive 
senescence  of  the  race  or  colony  occurs.  This  is  apparently  the 
case  among  both  plants  and  animals,  but,  as  already  pointed  out, 
experimental  investigation  has  shown  for  many  of  these  cases  that 
under  the  proper  conditions  progressive  senescence  does  not  occur, 
and  these  results  make  it  probable  that  we  shall  find  this  true  for 
many  other  cases.  It  may  be,  however,  that  in  some  forms  senes- 
cence progresses  in  spite  of  agamic  reproduction  and  independently 
of  external  conditions,  and  if  so  the  agamic  period  must  in  any  case 
sooner  or  later  come  to  an  end  in  such  forms.  Perhaps  some  of 
the  higher  animals,  where  agamic  reproduction  occurs  only  as 
polyembryony  or  in  the  early  stages  of  postembryonic  life,  consti- 
tute cases  of  this  sort. 

The  point  of  chief  importance  is,  however,  that  the  difference 
between  agamic  and  gametic  reproduction  is,  as  regards  the  rela- 
tion between  senescence  and  rejuvenescence,  one  of  degree  rather 


REJUVENESCENCE  IN  EMBRYO  AND  LAR\A  427 

than  of  kind,  and  that  there  is  much  more  (Hffercnce  in  this  respect 
between  different  forms  of  agamic  reproduction  than  between 
agamic  reproduction  from  single  cells  and  small  cell  masses  and 
gametic  reproduction.  From  the  physiological  point  of  view  the 
reproductive  process  is  fundamentally  the  same  wherever  it  occurs 
in  nature :  it  is  in  all  cases  the  reconstitution  of  a  new  organism  from 
a  part  of  one  previously  existing,  but  the  starting-point  of  the  new 
individual  and  consequently  the  degree  of  reconstitution  and  the 
result  differ  in  different  forms  and  with  different  conditions. 

CONCLUSION 

It  is  only  necessary  to  point  out  the  close  agreement  between 
all  the  different  lines  of  evidence  in  indicating  that  the  early  stages 
of  development  from  the  egg  in  both  animals  and  plants  constitute 
a  period  of  rejuvenescence  in  every  sense.  Minot  ('08)  has  already 
advanced  this  view  on  the  basis  of  the  changes  in  the  nucleoplasmic 
relation,  but  has  failed  to  present  any  of  the  physiological  evidence 
in  support  of  it.  The  nucleoplasmic  relation  is  a  rather  unsafe 
criterion  of  physiological  age,  but  it  is  interesting  to  see  that  in  the 
present  case  it  leads  to  the  same  conclusion  as  the  physiological 
evidence. 

From  this  point  of  view  gametic  reproduction  differs  from 
agamic  only  in  the  greater  degree  of  specialization  of  the  reproduc- 
tive cells  and  the  special  conditions  necessary  to  initiate  the  pro- 
cess of  dedifferentiation  and  rejuvenescence.  The  same  periodic 
changes,  the  same  Ufe  cycle  and  age  cycle,  occur  in  both.  We 
can  dispense  entirely  with  that  remarkable  conception,  the  germ 
plasm  of  the  Weismannian  theory,  and  say  that  germ  plasm  is 
any  protoplasm  capable  under  the  proper  conditions  of  undergoing 
dedifferentiation  and  reconstitution  into  a  new  individual  of  the 
species.  Reproduction,  whether  it  is  the  process  of  reconstitution 
in  a  piece  experimentally  isolated  from  an  animal  or  plant  body, 
or  the  process  of  development  from  the  fertilized  egg,  is  funda- 
mentally the  same  physiological  process  and  involves  both  regressive 
and  progressive  changes,  both  rejuvenescence  and  senescence. 

A  recent  attempt  by  Godlewski  ('10)  to  compare  the  process  of 
regeneration  with   gametic   reproduction   requires   mention   here. 


428  SENESCENCE  AND  REJUVENESCENCE 

Godlewski  found  that  in  the  earlier  stages  of  regeneration  the 
epithelial  cells  of  amphibia  show  an  increase  in  cytoplasmic  in 
relation  to  nuclear  volume  as  compared  with  the  cells  of  differen- 
tiated normal  epithelium,  and  that  the  nucleoplasmic  relation 
gradually  approaches  the  norm  as  regeneration  proceeds.  From 
these  facts  he  concludes  that  the  earher  stages  in  regeneration  cor- 
respond to  the  period  of  oogenesis,  and  particularly  that  stage  of 
it  in  which  the  egg  cytoplasm  increases  in  amount,  while  the  later 
stages  of  regeneration  correspond  to  the  period  of  embryonic 
development  in  which  nuclear  substance  undergoes  relative  increase. 
These  conclusions  only  serve,  I  think,  to  show  how  unsafe  the 
nucleoplasmic  relation  is  as  a  criterion  of  physiological  condition. 
It  is  probable  that  the  first  effect  of  stimulation  and  increase 
in  metabolic  rate  in  these  cells  is  some  degree  of  hypertrophy 
(pp.  43-44)  with  increase  in  the  relative  volume  of  cytoplasm,  but 
this  is  soon  followed  by  divisions  with  increase  in  relative  nuclear 
volume.  This  is  the  period  of  dedift'erentiation  and  rejuvenescence 
and  corresponds  not  to  the  growth  period  of  the  egg,  but  to  the 
period  of  rejuvenescence  in  embryonic  development,  while  the  later 
stages  of  regeneration  correspond  to  the  period  of  morphogenesis 
and  senescence  in  the  later  stages  of  development. 

REFERENCES 

BUGLIA,  G. 

1908.  "SuUo  scambio  gassoso  delle  uove  di  'Aplysia  limacina'  nei  vari 
period!  dello  sviluppo,"  Arch,  difisiol.,  V. 

CONKLIN,  E.  G. 

1912.     "Cell  Size  and  Nuclear  Size,"  Jour,  of  Exp.  ZooL,  XII. 
Crocker,  W. 

1906.  "Role  of  Seed  Coats  in  Delayed  Germination,"  Bot.  Gazette,  XLII. 

1907.  "Germination  of  Seeds  of  Water  Plants,"  Bot.  Gazette,  XLIV. 

1909.  "Longevity  of  Seeds,"  Bot.  Gazette,  XL VII. 
Erdmann,  Rhoda. 

1908.  "Experimentelle  Untersuchung  der  Massenverhaltnisse  von 
Plasma,  Kern  und  Chromosomen  in  dem  sich  entwickelnden 
Seeigelei,"  Arch.  f.  Zellforsch.,  II. 

Godlewski,  E.,  Jr. 

1908.  "  Plasma  und  Kernsubstanz  in  der  normalen  und  der  durch  aussere 
Faktoren  veranderten  Entwicklung  der  Echiniden,"  Arch.  /. 
Entwickelungsmech . ,  XXVI . 


REJUVExXESCExN'CE  IN  EMIiRVO  AND  LAR\A  429 

GODLEVVSKI,  E.,  Jr. 

1910.     "Plasma  und  Kernsubstanz  im  Epilhelgcwcbc  bei  dcr  Regeneration 
der  Amphibien,"  Arch.  J.  Etitwickdungsmcch.,  XXX. 
Harvey,  E.  N. 

1910.     "Methods  of  Artificial  Parthenogenesis,"  Biol.  Bull.,  X\III. 
Jennings,  H.  S. 

1913-     "The  Effect  of  Conjugation  in  Paramecium,"  Jour,  of  Exp  Zool 
XIV. 

Loeb,  J. 

1910.  "Die  Hemmung  verschiedener  Giftwirkungcn  auf  das  befruchtete 
Seeigelei  durch  Hemmung  der  Oxydationen  in  demsclben," 
Biochem.  Zeilschr.,  XXIX. 

1911.  "Auf  welcher  Weise  rettet  die  Befruchtung  das  Leben  des  Eies  ?" 
Arch.  f.  Entwickelungsmcch.,  XXXI. 

Loeb,  J.,  und  Wasteneys,  H. 

1910.  "Warum  hemmt  Natriumcyanide  die  Giflwirkung  einer  Chlor- 
natriumlosung    fur   das  Seeigelei?"  Biochem.  Zcitschr.,  XX\'III. 

1911.  "Sind  die  O.xydationsvorgiinge  die  unabhangige  Variable  in  den 
Lebensercheinungen  ?"  Biochem.  Zeilschr.,  XXX\'I. 

191 2.  "Die  Oxydationsvorgange  im  bcfruchteten  und  unbefruchteten 
Seesternei,"  Arch.  f.  Enlwickelungsmech.,  XXXV. 

Lyon,  E.  P. 

1902.    "Eflfects  of  Potassium  Cyanide  and  of  Lack  of  Oxygen  upon  the 
Fertilized  Eggs  and  the  Embryos  of  the  Sea  Urchin   (Arbacia 
punctulala),"  Am.  Jour,  of  Physiol.,  VII. 
Mathews,  A.  P. 

1901.     "Artificial  Parthenogenesis  Produced  by  Mechanical  .Agitation," 
Am.  Jour,  of  Physiol.,  VI. 
Meyerhof,  O. 

1911.     "  Untersuchungen  uber  die  Wiirmetonung  der  vitalen  Oxydations- 
vorgange in  Eiern,  I-III,"  Biochem.  Zeilschr.,  XXX\'. 
Minot,  C.  S. 

1908.     The  Problem  of  Age,  Growth  mid  Death.     New  York. 
Warburg,  O. 

1908.     "Beobachtungen     uber    die    Oxydationsprozesse    im    Seeigelei," 

Zeilschr.  f.  physiol.  Chcm.,  LVII. 
1910.     "Uber  die  O.xydationen  in  lebenden  Zellcn  nach  \'crsuchcn  am 
Seeigelei,"  Zeilschr.  f.  physiol.  Chem.,  LX\'I. 
Wilson,  E.  B. 

1892.     "The  Cell-Lineage  of  Nereis,"  Jour,  of  MorphoL,  \'I. 


PART  V 
THEORETICAL  AND  CRITICAL 


CHAPTER  X\l 
SOME  THEORIES  OF  SENESCENCE  AND  REJUVENESCENCE 

The  present  chapter  makes  no  attempt  at  a  com])lcte  historical 
review  of  the  various  ideas  and  theories  concerning  the  nature 
of  the  age  process:  it  is  merely  a  brief  critical  consideration,  in 
the  light  of  the  preceding  experimental  data,  of  some  of  the  more 
recent  theories  and  suggestions. 

SENESCENCE  AS  A  SPECIAL  OR  INCIDENTAL  FEATURE  OF  LIFE 

The  popular  belief,  which  is  of  course  based  on  the  phenomena 
of  old  age  and  death  in  man  and  the  higher  animals,  is  that  the 
process  of  aging  is  a  wearing  out  and  death  a  final  breakdown  of  the 
organic  mechanism,  or  some  essential  part  of  it.  This  idea  has 
from  time  to  time  found  scientific  support,  chiefly  among  those 
who  have  considered  the  problem  of  senescence  primarily  in  rela- 
tion to  man.  Among  the  earlier  authorities  of  the  modern  era  in 
science  Lotze  ('51,  '84)  is  one  who  holds  this  view,  and  recently 
Alagnus-Levy  ('07)  has  expressed  the  same  opinion.  While  the 
phenomena  of  senile  atrophy  in  extreme  old  age  in  man  and  the 
higher  animals  may  perhaps  be  interpreted  as  in  some  sense  a 
wearing  out  (see  pp.  288-89),  they  represent  only  the  final  stages 
of  senescence  and  are  the  result  of  what  has  happened  during  the 
earlier  life  of  the  organism.  Both  man  and  animals  grow  old 
throughout  the  course  of  progressive  development,  as  the  decrease 
in  rate  of  metabolism  indicates. 

Speculative  attempts  have  been  made  to  show  that  age  and 
death  are  associated  in  some  way  with  the  reproductive  function. 
Weismann  regards  the  limitation  of  life  as  an  adaptation  which  has 
arisen  by  the  action  of  natural  selection,  because  continued  life  of 
the  individual  after  the  reproductive  period  is  a  ''senseless  luxury" 
for  the  species.  Weismann's  views  arc  discussed  in  another 
chapter  (see  pp.  304-5).  In  opposition  to  this  hypothesis  Goette 
{'Ss)  maintains  that  reproduction  is  the  real  cause  of  age  and  death 
of  the  parent  individual  and  at  the  same  time  brings  about  rejuve- 
nescence in  the  offspring.     The  foundation  of  Goette's  hypothesis 

433 


434  SENESCENCE  AND  REJUVENESCENCE 

is  the  fact  that  reproduction  in  many  of  the  simpler  organisms 
inv^olves  a  disintegration  of  the  original  individual  and  the  origin 
of  new  individuals  from  its  parts  or  certain  of  them.  According 
to  von  Hansemann  ('93,  '09),  it  is  the  atrophy  of  the  sexual  organs, 
the  final  ehmination  of  the  germ  plasm,  which  brings  about  the 
changes  of  old  age  ending  in  death.  These  hypotheses  are  little 
more  than  guesses  based  on  observation  of  the  Hfe  histories  of 
various  organisms. 

Various  authors  have  suggested  that  conjugation  and  fertihza- 
tion  bring  about  rejuvenescence  in  some  way.  Maupas  ('88,  '89) 
believed  that  the  infusoria  grow  old  and  may  finally  die  of  old  age 
in  the  course  of  repeated  agamic  reproductions  and  that  conjuga- 
tion renews  their  capacity  for  growth  and  division,  but  later 
investigators  do  not  confirm  these  conclusions  (see  pp.  136-45). 
Bernstein  ('98)  suggests  that  certain  internal  conditions  whose 
nature  is  unknown  act  as  inhibitors  of  the  growth  impulse,  and 
that  their  effect  increases  during  life  and  finally  brings  about  death. 
Fertihzation,  however,  weakens  or  inhibits  the  inhibitors,  and 
growth  proceeds  anew  until  again  gradually  inhibited.  According 
to  Biihler  ('04)  the  molecular  constitution  of  the  organic  substance 
undergoes  gradual  change  during  life  and  becomes  less  and  less 
capable  of  metabolism,  and  fertilization  re-establishes  the  original 
constitution.  Rubner  ('89)  has  advanced  a  very  similar  \dew. 
These  hypotheses  are  merely  statements  of  a  supposed  fact  and  do 
not  throw  any  fight  upon  the  problem  of  the  nature  of  the  processes 
concerned  in  either  senescence  or  rejuvenescence. 

The  idea  that  age  and  death  are  the  results  of  an  intoxication, 
a  poisoning  of  the  organism  in  one  way  or  another,  has  been  ad- 
vanced by  various  authors,  among  whom  Metchnikoff  ('03,  '10) 
has  received  most  attention.  According  to  Metchnikoff"  man  is 
slowly  poisoned  by  resorption  of  the  products  of  bacterial  activity 
in  the  large  intestine.  One  result  of  this  intoxication  is  arterio- 
sclerosis; another  is  that  some  of  the  phagocytes,  the  white  blood 
corpuscles,  under  the  influence  of  the  poisons  depart  from  their 
proper  function  as  scavengers  and  protectors  of  the  tissues  and 
begin  to  devour  the  cells  of  the  highest  organs  of  the  body,  even 
those  of  the  nervous  system.     While  ]\Ietchnikoff''s  ideas  have 


SOME  CURRENT  THEORIES 


435 


aroused  great  popular  interest,  largely  because  of  his  scheme  for 
prolonging  life  by  preventing  the  intestinal  intoxications,  they 
have  received  little  support  among  scientists.  The  evidence  for 
the  universal  or  almost  universal  occurrence  of  chronic  intoxica- 
tion in  man,  and  of  arteriosclerosis  as  a  result  of  it,  is  far  from 
convincing,  and  the  hypothesis  of  the  action  of  the  phagocytes 
under  such  conditions  has  proved  even  less  acceptable.  At  best 
Metchnikoff' s  hypothesis  is  not  widely  applicable,  for  many  animals 
which  possess  no  large  intestine  grow  old  and  die.  But,  as  is  evi- 
dent from  his  statement  that  natural  death  occurs  very  rarely, 
Metchnikoff  is  really  concerned  with  certain  pathological  aspects 
of  advanced  life  in  man  and  not  at  all  with  the  problem  of  physio- 
logical senescence.  While  his  ideas  may  or  may  not  be  of  practical 
value,  they  have  no  general  theoretical  significance. 

According  to  Jickeli  ('02)  metabolism  is  an  incomplete  process 
and  injurious  substances  accumulate  in  the  cell  because  of  this 
incompleteness  of  metabolism.  The  secretions  of  cuticular  sub- 
stances, cysts,  cellulose  membranes,  etc.,  the  formation  of  hair, 
feathers,  and  various  other  products  of  cellular  activity  represent 
these  injurious  substances  of  which  the  cell  attempts  to  rid  itself 
by  excretion,  or  the  body  by  giving  rise  to  parts  which  are  sooner 
or  later  cast  off.  In  other  cases  the  cells  react  to  the  accumulation 
of  injurious  substances  by  increased  rate  of  division,  which  results 
in  increase  of  surface  and  so  in  greater  possibility  of  excretion. 
The  accumulation  of  the  injurious  substances  brings  about  senes- 
i^ence  and  death,  and  excretion  by  the  cell,  or  the  casting  off  of 
parts  by  the  organism,  is  a  process  of  rejuvenescence.  This 
hypothesis  is  based  entirely  on  a  teleological  conception  of  the  cell 
and  the  organism  and  cannot  be  regarded  as  in  any  real  sense 
physiological,  although  in  his  fundamental  idea  that  senescence 
results  from  accumulation  of  substances  in  the  cell  and  rejuvenes- 
cence from  their  eHmination  Jickeli  approaches  my  own  position. 
But  for  him  the  substances  concerned  are  not  the  protoplasmic 
substratum  of  the  cell,  but  something  ''injurious''  which  remains 
in  the  cell  only  because  metabolism  is  an  incomplete  process,  and 
the  cell  and  the  organism  are  all  the  time  struggling,  apparently  with 
superhuman  intelligence,  to  rid  themselves  of  their  burdens. 


436  SENESCENCE  AND  REJUVENESCENCE 

More  recently  Montgomery  ('06)  advanced  a  somewhat  simi- 
lar hypothesis.  He  beheved  that  waste  products  accumulate  in 
the  cells  as  life  continues  and  that  some  of  them  are  toxic.  Senes- 
cence and  death  are  the  result  of  the  insufficiency  of  the  excretion 
process.  Reproduction  is  in  general  an  escape  or  separation  of  some 
parts  from  "an  empoisoned  mass,"  and  the  part  which  is  thus 
separated  is  capable  of  repeating  the  hfe  history.  But  Mont- 
gomery does  not  make  it  clear  why  the  part  or  parts  which  separate 
as  reproductive  elements  do  not  carry  their  share  of  the  poisonous 
substances  with  them.  This  is  the  most  important  point,  for  if 
the  reproductive  elements  do  not  free  themselves  from  these  poisons 
they,  as  well  as  other  parts,  must  die,  and  there  seems  to  be  no 
reason  except  a  teleological  one  why  parts  should  separate  as  repro- 
ductive elements  at  all.  Here,  as  in  Jickeli's  hypothesis,  certain 
cells  free  themselves,  voluntarily  as  it  were,  from  the  poisonous 
substances  which  are  killing  the  organism.  The  chief  difference 
between  Jickeli  and  Montgomery  is  that  for  the  one  rejuvenescence 
is  an  excretory  process  and  may  occur  in  somatic  as  well  as  in 
reproductive  cells,  while  the  other  maintains  that  only  the  repro- 
ductive elements  rejuvenate,  and  that  they  somehow  leave  the 
poisonous  substances  behind  in  the  body  or  in  a  residuum. 

SENESCENCE   AS   A   RESULT   OF    ORGANIC   CONSTITUTION 

Most  of  those  who  have  considered  the  problem  of  age  from  any 
general  viewpoint  have  maintained  that  the  conditions  which 
determine  senescence  and  death  are  found  in  the  physiological 
constitution  of  the  organism.  Seventy  years  ago  Johannes  Muller 
('44)  expressed  this  opinion;  some  forty  years  later  Cohnheim  {'82) 
took  the  same  position,  and  in  more  recent  years  this  view  has  found 
numerous  supporters. 

Butschli's  suggestion  ('82)  that  death  is  due  to  the  exhaustion 
of  the  supply  of  a  certain  substance — the  "life  ferment" — which  is 
gradually  used  up  during  life,  and  that  the  protozoa  and  the  germ 
cells  of  multicellular  forms  do  not  die  because  they  are  capable  of 
producing  the  substance  anew,  is  not  much  more  than  a  statement 
that  death  is  the  result  of  life  without  rejuvenescence.  Cholod- 
kowsky  ('82),  on  the  other  hand,  suggested  that  death  was  rather 


SOME  CURRENT  THEORIES  437 

the  result  of  the  multicellular  condition  with  its  accompanying 
differentiation.  In  such  organisms  the  struggle  for  existence  among 
the  parts  which  Roux  ('81)  believed  to  be  of  such  fundamental 
importance  in  organic  life  must  lead  linally  to  the  death  of  the 
whole. 

The  change  in  the  relation  between  surface  and  volume  in  the 
cell  and  the  organism  during  growth  has  often  served  as  the  founda- 
tion for  speculations  concerning  growth  and  its  cessation,  aging  and 
death,  and  cell  division.  Since  the  volume  of  the  cell  or  the 
organism  increases  more  rapidly  than  its  surface,  and  since  nutrition 
and  oxygen  enter  through  the  surface,  it  is  argued  that  as  the  cell 
or  the  organism  increases  in  size  the  amount  of  nutrition  and  o.xy- 
gen  which  can  enter  through  the  surface  must  become  less  and  less 
adequate  for  the  needs  of  the  growing  cell  mass.  Sooner  or  later 
a  stage  may  be  reached  where  only  the  superficial  parts  of  the  cell 
receive  sufficient  nutrition,  and  finally  the  death  of  the  cell  may 
result  from  the  starvation  of  the  parts  farthest  from  the  surface. 
Various  authors,  among  them  Herbert  Spencer,  Bergmann  and 
Leuckart,  and  later  Verworn,  have  called  attention  to  the  biological 
importance  of  this  relation  between  surface  and  volume  and  have 
employed  it  as  a  basis  for  theoretical  considerations  concerning 
one  aspect  or  another  of  life.  Recently  Muhlmann  ('00,  '10.  '14) 
has  advanced  a  theorj'  of  senescence  and  death  based  upon  this 
principle.  According  to  Miihlmann  growth  brings  about  senescence 
and  death  because  it  leads  sooner  or  later  to  star\'ation  of  the  parts 
of  the  cell  or  the  organism  farthest  from  the  surface.  In  the  uni- 
cellular forms  the  nucleus  reacts  to  the  extreme  stage  of  starvation 
by  division,  which  is  followed  by  cell  division,  and  so  an  increase 
of  nutritive  surface  is  produced;  but  in  multicellular  organisms, 
where  the  cells  do  not  separate  from  each  other,  cell  division  only 
leads  to  further  growth  and  so  to  starvation,  which  is  most  extreme 
in  the  part  farthest  from  the  surface.  Old  age  is  then  a  comlition 
of  starvation  which  according  to  Miihlmann  is  most  extreme  in  the 
central  nervous  system,  the  part  farthest  removed  from  the  nutri- 
tive surfaces,  and  death  is  consequently  primarily  a  death  of  the 
nervous  system.  Death  for  Miihlmann  is  not  only  the  cessation 
of  life,  as  it  occurs  in  man  and  the  higher  animals,  but  the  division 


438  SENESCENCE  AND  REJUVENESCENCE 

of  the  cell  is  the  death  of  the  individual  cell.  The  changes  in  the 
cells  during  their  development,  the  appearance  of  metaplasmic 
structural  substances,  which  is  usually  regarded  as  differentiation, 
IMiihlmann  interprets  as  a  dedifferentiation  and  regression  from 
the  embryonic  condition  and  as  a  secondary  result  of  the  gradual 
starvation  of  the  cells. 

As  regards  the  biological  importance  of  the  relation  between 
surface  and  volume,  I  am  not  aware  that  it  has  been  proved  in 
any  case  to  be  a  fundamental  factor  in  limiting  growth.  Growth 
is  not  simply  a  matter  of  nutrition:  in  the  higher  animals  a  very 
definite  limit  of  size  exists,  no  matter  how  great  the  supply  of 
nutrition,  and  in  many  lower  animals  extensive  reconstitutional 
growth  may  occur,  even  in  a  stage  of  extreme  reduction  from  star- 
vation. On  the  other  hand,  the  growth  of  embryonic  cells  may 
be  inhibited  by  correlative  influences  from  other  parts,  even 
though  an  abundant  supply  of  nutrition  is  present.  In  many  cases 
animal  eggs  receive  their  nutrition  chiefly  or  wholly  through  a 
minute  fraction  of  their  surface  (see  Figs.  184,  185,  p.  345)  yet 
are  able  to  attain  an  enormous  size  as  compared  with  other  cells 
of  the  body.  Similarly,  in  many  cells  of  the  multicellular  body, 
the  nutritive  surface  is  evidently  only  a  small  fraction  of  the  total 
surface  of  the  cell,  e.g.,  in  many  glandular  tissues,  yet  life  and 
function  continue.  And  in  the  unicellular  infusoria  food  enters 
through  a  definite  mouth  and  passes  into  the  entoplasm,  where  a 
nutritive  surface  is  formed  about  each  food  particle.  In  such  cases 
the  external  surface  of  the  cell  has  no  relation  to  its  capacity  for 
ingesting  food.  Oxygen  doubtless  enters  through  the  cell  surface, 
but  it  undoubtedly  enters  more  or  less  rapidly  according  to  con- 
ditions in  the  cell.  In  fact,  the  whole  theory  of  the  biological 
importance  of  the  relation  between  surface  and  volume  rests  rather 
upon  a  process  of  logic  than  upon  the  data  of  observation  and 
experiment,  and  when  we  examine  the  behavior  of  cells  and  organ- 
isms it  is  difficult  to  find  adequate  support  for  it. 

As  regards  Miihlmann's  hypothesis,  the  conclusion  that  old  age 
is  an  advanced  stage  of  cell  starvation  rests  chiefly  upon  assertion 
rather  than  proof.  As  a  matter  of  fact,  in  starvation  the  nervous 
system  loses  less  than  other  tissues,  while  in  old  age,  according  to 


St)MK  CURRKXT  THKORIES 


439 


Miihlmann,  it  suffers  most  of  all.  That  accumulation  of  structural 
substance  and  so-called  metaplasm  in  the  cells  is  the  result  of  a 
gradual  starvation  is  difticult  to  believe  in  view  of  the  fact  that 
during  actual  starvation  in  the  lower  animals  these  substances  may 
disappear  to  a  greater  or  less  extent.  And  the  fact  that  cell  division 
can  be  inhibited  by  starvation  is  scarcely  in  agreement  with  Miihl- 
mann's  assertion  that  cell  division  results  from  starvation  of  the 
nucleus.  ^Miihlmann  regards  all  that  is  commonly  called  progres- 
sive development  as  a  regression  or  involution  from  the  embryonic 
condition  and  maintains  that  the  only  progress  is  the  reproduction 
of  embryonic  cells,  but  here  again  we  have  merely  assertion,  not 
evidence.  In  what  way  progress  is  involved  in  the  reproduction 
of  embryonic  cells  he  does  not  attempt  to  show.  And  his  assertion 
that  cell  division  and  the  cessation  of  life  are  both  death  leaves  the 
idea  of  death  without  any  physiological  significance,  for  cell  division 
and  the  cessation  of  Hfe  are  certainly  two  very  ditTerent  processes. 
In  the  one  an  increase  in  metabolism  apparently  occurs,  while  in 
the  other  metabolism  ceases. 

]More  than  twenty  years  ago  Richard  Hertwig  ('89)  advanced  the 
opinion,  based  on  studies  of  certain  protozoa,  that  "depression  "  and 
"physiological  degeneration"  of  the  cell — conditions  supposedly 
more  or  less  closely  identical  with  senescence  and  natural  death — 
are  associated  wdth  an  increase  in  the  size  of  the  nucleus  relatively 
to  the  cytoplasm,  and  in  later  papers  ('03,  '08)  he  has  attempted  to 
show  that  the  nucleoplasmic  relation,  i.e.,  the  size  ratio  of  nucleus 
to  cytoplasm,  varies  and  regulates  itself  within  definite  limits  for 
each  particular  kind  of  cell  and  that  its  variation  is  an  index  of 
the  functional  condition  of  the  cell.  This  idea  has  been  further 
developed  by  some  of  his  students  and  others,  but  has  also  been 
rather  widely  criticized,  and  many  investigators  have  not  been 
able  to  find  the  detiniteness  of  relation  which  Hertwig  believes  io 
exist.  Conklin  ('12),  for  example,  concludes  from  an  extensive 
study  of  the  nucleoplasmic  relation  in  the  development  of  the 
mollusk  Crcpidula,  that  it  is  neither  a  constant  nor  a  self-regulating 
ratio  and  not  a  cause  of  cell  division,  as  Hertwig  believes,  but 
rather  a  result.  As  a  matter  of  fact  differentiation  and  senescence 
in  the  higher  animals  arc  associated  in  most  tissues  with  an  increase 


440  SENESCENCE  AND  REJUVENESCENCE 

in  the  relative  volume  of  the  cytoplasm  rather  than  of  the  nucleus. 
Hertwig  assumes  that  the  cell  is  able  to  regulate  its  own  nucleo- 
plasmic  relation,  at  least  within  certain  limits,  but  the  origin  and 
nature  of  the  nucleoplasmic  tension  which  he  postulates  as  the 
basis  of  this  regulation,  as  well  as  the  physiological  mechanism  of 
regulation,  remain  obscure.  In  short,  the  hypothesis  has  not  a 
physiological  foundation  and  apparently  is  not  in  complete  agree- 
ment with  the  facts. 

Minot's  views,  which  are  fully  stated  in  his  recent  pubhcations 
(Minot,  '08,  '13),  are  almost  diametrically  opposed  to  those  of 
Hertwig,  as  regards  the  direction  of  change  in  the  nucleoplasmic 
relation  during  senescence.  Minot  attempts  to  show  that  the 
growth  and  differentiation  of  the  cytoplasm  are  the  fundamental 
factors  in  senescence  and  death.  In  the  young  cell  the  amount  of 
cytoplasm  in  relation  to  the  amount  of  nuclear  substance  is  least, 
but  during  development  it  increases  and  undergoes  differentiation^ 
" cy tomorphosis  "  occurs,  and  brings  about  senescence. 

According  to  Minot  this  is  a  universal  law,  but  his  evidence  is 
taken  almost  entirely  from  the  higher  animals.  In  many  of  the 
lower  animals  no  marked  proportional  increase  in  the  amount  of 
cytoplasm  occurs  during  development,  and  in  the  plants  differ- 
entiation is  in  genera]  accompanied,  not  by  increase  in  the  cyto- 
plasm, but  by  vacuoHzation.  Therefore  the  size  relations  of  the 
cytoplasm  and  nucleus,  while  they  may  serve  to  some  extent  as  an 
index  of  age  in  the  higher  animals,  cannot  by  any  means  be  regarded 
as  a  universal  factor  in  senescence.  But  the  differentiation  of  the 
cytoplasm  undoubtedly  is  a  very  important  factor  in  senescence, 
and  as  regards  this  point  my  own  view  agrees  closely  with  Minot's. 

The  changes  in  the  substratum  of  the  cells  are  merely  the  con- 
ditions or  one  aspect  of  senescence,  they  are  not  senescence  itself,, 
for  that  is  a  change  in  the  dynamic  processes  of  the  organism  which 
ends  in  their  cessation.  Minot,  however,  has  not  told  us  what 
senescence  is  nor  how  the  cytoplasmic  changes  bring  it  about.  I 
have  attempted  to  show  that  senescence  is  a  decrease  and  rejuve- 
nescence an  increase  in  rate  of  metabolism  associated  with  changes 
in  the  cellular  substratum  which  themselves  result  from  the  relation 
between  substratum  and  metabohsm   (Child,   '11,   '14).     In  his 


SOME  CURRENT  THEORIES  44  i 

latest  paper  Minot  has  criticized  this  view  on  the  grcjund  that  if  it 
were  correct  we  must  be  growing  alternately  old  and  young.  While 
I  am  quite  ready  to  admit  that  this  is  to  a  certain  extent  the  case, 
it  does  not  by  any  means  follow,  as  Minot  has  asserted,  that  every 
change  in  metabolic  rate  is  either  senescence  or  rejuvenescence. 
Undoubtedly  it  is  often  impossible  to  draw  a  sharp  line  of  distinc- 
tion between  the  age  changes  and  many  other  periodic  changes  in 
the  organism  (see  pp.  187-93),  y^^  in  general  senescence  and  reju- 
venescence are  relatively  slow  and  gradual  changes  in  metabolic 
rate  associated  with  certain  changes  in  the  cellular  substratum, 
which  do  not  undergo  rapid  reversal  or  regression.  Minot's  criti- 
cism is  quite  beside  the  point.  There  is  nothing  in  his  own  theory 
that  is  in  conflict  in  any  way  with  the  idea  that  senescence  and 
rejuvenescence,  viewed  in  their  dynamic  aspects,  are  changes  in 
rate  of  metabolism,  for  it  is  concerned  with  certain  conditions  and 
indications  of  senescence  in  the  cells  rather  than  with  the  process 
of  senescence  itself. 

According  to  iMinot,  dediffercntiation  and  rejuvenescence  do 
not  occur  in  the  body  cells.  At  various  points  in  the  present  book 
(see  especially  chaps,  v-vii,  x,  xii)  I  have  endeavored  to  show  that 
dediffercntiation  and  rejuvenescence  occur  very  widely  in  body 
cells.  No  further  discussion,  therefore,  is  necessary  here.  Minot 
believes,  however,  that  the  egg  dififers  from  all  other  cells  in  that  it 
undergoes  rejuvenescence  after  fertilization.  The  basis  for  this 
conclusion  is  the  increase  during  this  stage  in  the  amount  of 
nuclear  substance  in  relation  to  cytoplasm.  As  regards  the 
occurrence  of  rejuvenescence  in  the  embr^'o,  I  am  in  essential 
agreement  with  him,  but  my  conclusions  are  based  on  the  changes 
in  metabolic  rate  rather  than  size  relations  of  nucleus  and  cyto- 
plasm. IMinot,  however,  has  made  no  mention  of  the  spermatozoon. 
According  to  his  view  it  should  be  one  of  the  youngest  cells  in 
existence,  since  it  possesses  in  most  cases  practically  no  cytoplasm. 
As  a  matter  of  fact,  however,  it  shows  none  of  the  characteristics 
of  a  young  cell.  It  is  if  anything  more  highly  specialized  than  the 
egg,  and  has  ceased  entirely  to  grow;  moreover,  when  it  enters  the 
egg  it  loses  its  morj^hological  characteristics  and  to  all  apix-arances 
also  undergoes  dedilTerentiation  and  rejuvenescence  into  an  ordinary 


442  SENESCENCE  AND  REJUVENESCENCE 

nucleus.  It  would  be  of  interest  to  know  how  Minot  regarded 
this  cell. 

Delage  ('03)  believes  that  age  and  death  are  the  result  of  differ- 
entiation. In  the  course  of  differentiation  the  cells  lose  the  capacity 
for  reproduction  and  finally  for  growth,  and  no  cell  is  able  to  live 
indefinitely  without  either  growing  or  dividing.  The  idea  that 
cell  reproduction  prevents  or  retards  senescence  seems  to  be  involved 
in  this  view,  but  Delage  does  not  attempt  to  develop  it. 

Jennings  has  recently  advanced  a  view  very  similar  to  that  held 
by  Delage.  Age  and  death,  according  to  Jennings  ('12,  '13),  are 
the  result  of  the  increased  differentiation  of  the  higher  organisms. 
The  infusoria  do  not  necessarily  die  or  undergo  progressive  race 
senescence,  as  Maupas  believed.  In  the  more  complex  and  highly 
organized  body  of  the  higher  animals  the  greater  degree  of  differ- 
entiation brings  about  loss  of  capacity  to  carry  on  the  fundamental 
vital  processes,  and  so  death  finally  results.  Jennings  fails  to 
note  that  the  higher  organisms  differ  from  the  protozoa,  not  merely 
in  the  degree  of  structural  dift'erentiation,  but  in  the  absence  or 
limitation  of  agamic  reproduction.  As  I  have  endeavored  to  show 
(pp.  136-45),  it  is  the  repeated  process  of  reproduction  rather  than 
their  low  degree  of  differentiation  which  prevents  progressive  race 
senescence  and  death  in  the  protozoa.  Each  division  brings  about 
some  degree  of  rejuvenescence,  which  may  balance  the  senescence 
during  the  interval  between  divisions.  Doubtless  the  capacity  of 
the  protozoa  to  reproduce  agamically  and  their  low  degree  of  dift'er- 
entiation  are  associated  with  each  other  as  results  of  a  common 
cause,  but  it  is  the  repeated  interruption  of  progressive  develop- 
ment by  regression  that  prevents  or  retards  old  age  and  death. 

It  remains  to  consider  certain  hypotheses  which  concern  them- 
selves more  directly  with  the  metabolic  aspects  of  the  age  changes. 
In  his  Allgemeine  Biologie  (1899),  Kassowitz  has  attempted  a 
general  consideration  of  biological  phenomena  on  the  basis  of  a 
theory  of  metabolism  which  assumes  that  all  metabolism  consists 
in  the  synthesis  and  destruction  of  the  protoplasm  molecule.  All 
non-protoplasmic  (metaplasmic)  substances,  such  for  example  as 
fat,  glycogen,  starch,  etc.,  which  appear  in  the  cell,  must  first  have 
formed  part  of  the  protoplasm  molecules,  and  their  formation  is  the 


SOME  CURRENT  THEORIES  443 

result  of  chemical  decomposition  of  these  molecules.  When  the 
cells  are  strongly  stimulated,  as  they  are  during  active  function, 
the  protoplasmic  molecules  break  down  into  substances  which  are 
eliminated  from  the  cell,  such  as  carbon  dioxide  and  the  nitrogenous 
excretion  products.  This  Kassowitz  terms  active  breakdown.  But 
even  when  the  cells  are  not  stimulated  and  functionally  active  to 
any  marked  degree,  protoplasmic  breakdown  still  occurs,  although 
slowly  and  incompletely,  and  this  inactive  breakdown  gives  rise  in 
large  part  to  the  metaplasmic  substances  which  accumulate  in  the 
cell.  The  metaplasmic  substances  are,  according  to  Kassowitz. 
either  quite  incapable  of  further  change  in  the  cell  after  they  are 
once  formed,  or  must  be  slowdy  transformed  by  the  action  of 
enzymes  before  they  can  again  take  part  in  the  synthesis  of  new 
protoplasmic  molecules.  The  presence  of  these  metaplasmic 
substances  in  the  cell  interferes  with  the  passage  of  oxygen  to  the 
labile  molecules  and  with  the  transmission  of  stimuli  and  so  favors 
further  inactive,  as  opposed  to  active,  breakdown  of  protoplasmic 
molecules.  Consequently,  when  metaplasmic  substances  appear 
in  the  cell,  the  inactive  breakdown  increases  and  this  in  turn  leads 
to  further  accumulation  of  metaplasm  and  so  on.  The  result  is  a 
decrease  in  functional  activity  and,  sooner  or  later,  death.  From 
this  point  of  view  senescence  and  death  are  the  result  of  a  progres- 
sive increase  in  the  inactive  breakdown  and  the  metaplasmic  sub- 
stances formed  by  it.  Death  from  old  age  finds  its  determining 
factors  in  the  chemical  and  physical  constitution  of  protoplasm. 

In  this  theory  the  ideas  of  the  accumulation  of  substance  in  the 
cell  and  its  efTect  upon  metabolism  as  a  basis  for  senescence  is  very 
clearly  and  fully  developed.  And  while  there  are  various  reasons 
for  dissenting  from  Kassowitz'  theory  of  metabolism  based  on  the 
labile  protoplasmic  molecule  (see  pp.  13-18)  and  from  the  sharp 
distinctions  made  between  active  and  inactive  breakdown  and 
between  protoplasm  and  metaplasm,  we  can  agree  with  him  that 
senescence  and  death  are  fundamental  features  of  life  and  are 
associated  w-ith  an  increase  in  stability  of  substratum  of  the  cell. 

As  regards  rejuvenescence,  Kassowitz  is  much  less  clear, 
although  he  has  in  his  ideas  a  satisfactory  foundation  for  a  theory 
of  rejuvenescence.     In  referring  to  Wcismann's  ideas  concerning 


444  SENESCENCE  AND  REJUVENESCENCE 

the  immortality  of  the  protozoa,  he  points  out  that  since  a  rapid 
growth  of  protoplasm  precedes  each  cell  division,  and  since  growing 
protoplasm  with  its  large  volume  of  active  breakdown  is  an  unfavor- 
able substratum  for  the  accumulation  of  metaplasm,  therefore  when 
such  growth  occurs  the  organism  may  frequently  remain  young. 
He  apparently  fails  entirely  to  note  that,  according  to  his  own 
hypothesis,  elimination  from  the  cell  of  metaplasmic  substances 
should  make  the  cell  more  capable  of  active  breakdown,  and  so 
younger. 

Enriques  ('07,  '09)  lays  stress  upon  the  decrease  in  assimilatory 
capacity,  and  this  capacity  he  believes  decreases  as  differentiation 
increases.  Death  is  not  a  necessary  consequence  of  life,  for  the 
unicellular  forms  and  also  many  plants  may  continue  to  live  indefi- 
nitely. Enriques  cites  some  chemical  analyses  of  plants  in  support 
of  his  view  that  the  nitrogenous  substances  become  "diluted" 
during  development  by  the  deposition  in  the  cells  of  carbohydrates. 
Moreover,  he  finds  that  the  changes  in  the  nitrogenous  substances 
precede  the  changes  in  other  substances,  and  this  confirms  his 
belief  that  the  assimilatory  capacity  of  the  cells  decreases,  for  the 
nitrogenous  substance  is  the  assimilating  substance.  In  other 
words,  a  decrease  in  the  proportion  of  chemically  active  protoplasm 
occurs  during  development.  My  own  views  are  in  essential  agree- 
ment with  those  of  Enriques,  but  I  have  endeavored  to  proceed 
a  few  steps  farther  and  to  show  how  rejuvenescence  occurs  and  its 
significance  in  retarding  and  preventing  senescence  and  death. 

Conklin  ('12,  '13)  has  expressed  himself  as  in  essential  agreement 
with  my  own  conclusions  concerning  the  nature  of  senescence  and 
rejuvenescence,  but  he  lays  particular  emphasis  upon  the  inter- 
change between  nucleus  and  cytoplasm  as  the  fundamental  condi- 
tion of  constructive  metabohsm,  and  concludes  that  "anything 
which  decreases  the  interchange  between  nucleus  and  protoplasm 
leads  to  seniHty;  anything  which  increases  this  interchange  renews 
youth."  This  conclusion  seems  to  me  not  sufficiently  broad  in 
one  sense  and  too  broad  in  another.  It  can  scarcely  be  doubted 
that  at  least  some  degree  of  cytoplasmic  or  nuclear  senescence  may 
occur  independently  of  the  metabohc  interchange  between  nucleus 
and  cytoplasm,  perhaps  as  a  result  of  colloid  or  other  changes  in 


SOME  CURREXT  THEORIES  445 

the  substratum.  Such  a  change  will  doubtless  decrease  nucleo- 
plasmic  interchange,  but  this  decrease  will  be  secondary  rather  than 
primary  in  the  senescence  process.  Nucleoplasmic  interchange 
depends  upon  the  metabolic  conditions  in  the  cytoplasm  and  in  the 
nucleus  and  may  be  altered  by  changes  in  either  or  both.  The 
primary  metabohc  changes  of  age  must  occur  throughout  the  proto- 
plasm. On  the  other  hand,  to  say,  as  Conklin  does,  that  anything 
which  decreases  nucleoplasmic  interchange  leads  to  senility  and 
anything  which  increases  it  renews  youth  is  manifestly  not  true, 
for  low  temperature  may  decrease  and  high  temperature  increase 
the  interchange,  but  such  metabolic  changes  do  not,  properly 
speaking,  constitute  senescence  and  rejuvenescence,  although  they 
may  in  some  cases  result  sooner  or  later  in  one  or  the  other. 

The  advances  during  recent  years  in  our  knowledge  of  the 
colloids  and  the  very  natural  and  entirely  justifiable  desire  to  apply 
the  principles  and  conclusions  of  colloid  chemistry  to  the  Uving 
organism  have  led  various  authors  to  suggest  that  senescence  in 
organisms  is  fundamentally  a  colloid  change.  In  chaps,  i,  ii,  and 
viii  I  have  called  attention  to  these  colloid  changes  and  their  impor- 
tance for  the  problems  of  senescence  and  rejuvenescence.  It  can 
scarcely  be  doubted  that  the  colloid  substratum  of  the  organism 
does  undergo  changes  which  are  not  essentially  different  from  those 
in  non-living  colloids  and  that  such  changes  play  an  important 
role  in  the  process  of  senescence.  They  are  perhaps,  as  I  suggested 
(pp.  49-50),  the  primary-  changes  in  embryonic  protoplasm  which 
lead  to  decrease  in  metabolic  rate  and  so  initiate  the  processes  of 
differentiation  and  senescence.  But  something  more  than  these 
changes  is  involved  in  at  least  most  cases  of  senescence,  for  ditTer- 
entiation  occurs,  new  structural  substances  are  {produced  and 
accumulate  in  the  cell,  and  its  metabolic  activity  often  becomes 
very  different  in  character  from  that  of  the  embryonic  cell.  While 
these  changes  may  depend  in  large  measure  upon  colloid  changes, 
it  is  probable  that  changes  in  the  chemical  constitution  of  the 
substratum  may  also  contribute  to  its  increasing  stability  and  so 
play  a  part  in  senescence. 

The  occurrence  of  rejuvenescence  has  not,  so  far  as  I  know, 
been  considered  in  connection  with  the  suggestions  that  senescence 


446  SENESCENCE  AND  REJUVENESCENCE 

is  a  colloid  change,  but  from  this  point  of  view  rejuvenescence 
would  naturally  be  regarded  as  a  reversal  of  the  change  concerned 
in  senescence  in  consequence  of  altered  conditions.  As  I  have 
pointed  out  (pp.  56-57),  however,  rejuvenescence  is  not  necessarily 
a  reversal  of  senescence,  but  rather,  to  a  large  extent  at  least,  the 
substitution  of  a  new  substratum  or  protoplasm  for  the  old,  which 
may  serve  in  greater  or  less  part  as  a  source  of  energy  and  of 
material.  Here  certainly  chemical  decomposition  and  synthesis 
are  the  important  factors,  although  reversible  colloid  changes  may 
be  concerned  to  some  extent. 

Life  is  not  entirely  a  matter  of  colloid  condition,  nor  is  it  entirely 
a  matter  of  chemical  reaction:  it  is  rather  in  the  interrelations 
between  chemical  reaction  and  colloid  substratum  that  we  find  the 
fundamental  characteristics  of  life.  If,  as  I  have  attempted  to 
show,  the  age  cycle  is  life  itself,  viewed  from  a  certain  standpoint, 
we  must  look  to  these  interrelations  for  any  adequate  conception  of 
the  changes  of  senescence  and  rejuvenescence. 

THE  CONCEPTION  OF  GROWTH  AS  AN  AUTOCATALYTIC  REACTION  AND 
THE  RESULTING  THEORY  OF  SENESCENCE 

Within  the  last  few  years  various  authors'  have  suggested  that 

growth  is  essentially  an  autocatalytic  reaction.     Loeb  has  made 

this  suggestion  in  several  papers  concerning  the  process  of  nuclein 

synthesis  in  the  developing  egg,  and  Robertson,  Wolfgang  Ostwald, 

and  Blackman  have  attempted  to  show  that  the  processes  of  growth 

in  general   follow   the   laws   of   autocatalysis.     An   autocatalytic 

reaction  is  one  in  which  one  or  more  of  the  products  of  the  reaction 

act  as  catalyzers  and  so  increase  the  velocity  of  the  reaction.     In 

such  a  reaction  the  velocity  of  the  transformation  at  any  instant  is 

proportional  to  the  amount  of  material  undergoing  change  and  to 

the  amount  of  material  already  transformed.     This  remains  true 

until  products  of  the  reaction  begin  to  decrease  its  velocity.     The 

curve  of  such  a  reaction  is  in  general  an  S-shaped   curve,   hke 

Fig.  199,  at  first  concave  to  the  axis  of  ordinates  as  the  velocity  of 

reaction  increases  and  finally  becoming   convex  to   this  axis  as 

the  velocity  decreases. 

•  Blackman,  '09;  Loeb,  '06,  '08,  '09;  Wolfgang  Ostwald,  '08;  Robertson,  '08a, 
'o8^  '13. 


SOME  CURRENT  THEORIES 


447 


Grams 


is.ooo 


10,000 


S.ooo 


4,000 


3,000 


2,000 


1,000 


1 2345678910 
Months  (birth) 


Years  after  birth 


Fig.  199. — Cur\'e  of  human  growth  for  the  embryonic  period  and  the  first  four 
years  after  birth,  drawn  from  the  absolute  increments  of  weight  in  Tabic  XIII:  each 
vertical  inter\-al  indicated  on  the  axis  of  ordinates  represents  an  absolute  increase  of 
weight  of  1,000  grams;  on  the  axis  of  abscissae  the  ten  short  intervals  at  the  left  re|)re- 
sent  the  nine  months  of  the  embryonic  period  and  the  month  of  birth,  and  each  of 
the  following  intervals  represents  one  year. 


448  SENESCENCE  AND  REJUVENESCENCE 

If  growth  is  a  process  of  this  kind,  the  rate  of  growth  must 
increase  up  to  a  certain  maximum  as  growth  proceeds  and  then, 
after  maintaining  this  maximum  for  a  longer  or  shorter  time,  must 
decrease.  Both  Robertson  and  Ostwald  present  a  great  variety  of 
data  from  various  sources  to  support  their  conclusions,  and  many 
of  Ostwald's  curves  are  very  characteristic  curves  of  autocatalysis. 
Robertson  has  attempted  to  show  further  that  in  any  growth-cycle 
of  an  organism,  tissue,  or  organ,  the  maximum  increase  in  volume  or 
weight  in  a  unit  of  time  occurs  when  the  total  growth  of  the  cycle  is 
half  completed.  From  this  point  of  view  senescence  consists  merely 
in  the  retardation  during  the  later  stages  of  a  growth-cycle  of  the 
rate  of  reaction  by  the  accumulation  of  the  products  of  reaction. 
Senile  atrophy  and  death  are  not  a  feature  of  the  reaction  and  must 
be  due  to  special  conditions  not  directly  connected  with  growth. 
Rejuvenescence,  so  far  as  it  occurs,  must  consist  of  a  reversal  of  the 
reaction  and  consequently  a  removal  of  the  accumulated  products 
which  were  responsible  for  the  retardation. 

The  foundation  upon  which  this  conception  of  growth  rests 
consists  of  the  observational,  statistical  data  of  the  increments  of 
growth  or  of  certain  growth-components,  such  as  weight,  length, 
water-content,  etc.,  in  various  organisms.  Ostwald  has  shown  that 
the  absolute  increments  of  growth  or  growth-components  show  very 
generally  an  increase  during  the  earher  and  a  decrease  during  the 
later  portion  of  the  growth-cycle  under  consideration  and  so  when 
graphically  presented  appear  as  an  S-shaped  curve  like  the  curve 
of  autocatalysis.  Robertson's  conclusions  rest  on  the  same  basis 
as  Ostwald's.  Stated  in  general  terms  these  results  mean  simply 
that  up  to  a  certain  point,  the  larger,  or  heavier,  or  longer  the 
organism  becomes,  the  greater  its  absolute  increase  in  a  given  time, 
but  beyond  that  point  the  absolute  increase  in  a  given  time  becomes 
smaller,  although  the  total  size,  or  weight,  or  length  is  still  in- 
creasing. 

The  same  statistical  data  may  be  handled  in  another  way. 
From  the  absolute  increments  we  may  determine  the  relative 
increments  of  weight,  length,  etc.,  that  is,  the  increase  in  a  given 
period  of  time  in  proportion  to  the  weight  or  length  at  the  beginning 
of  that  time.     This  relative  increment  may  be  expressed  as  a  per- 


SOME  CURRENT  THEORIES 


449 


centage  of  the  total  weight  or  length  at  the  beginning  of  each  period 
and  may  be  called  for  convenience  the  percentage  increment.  The 
percentage  increments  for  different  periods  enable  us  to  compare 
the  activity  of  the  organic  substance  per  unit  of  weight  or  length 
in  adding  to  the  weight  or  length  in  each  period,  and  we  find  that 
in  growth  the  percentage  increments  may  decrease  while  the 
absolute  increments  are  still  increasing.  In  other  words,  as  growth 
proceeds,  the  absolute  increment  in  grams  or  millimeters  may 
become  greater,  but  the  growth-activity  of  each  unit  of  weight  or 
length  already  present  is  decreasing. 

TABLE  XIII 

Weights  of  the  Human  Embryo  axd  of  the  Child  during 
THE  First  Four  Years  after  Birth 


2  months 

3  "       

4  "       

5  "       

6  "       

7  "       

8  "       

9  "       

lo  "  (birth) 

5  year 

X  « 

2  

3  « 

4  ■ 

I  "       

li  "       

1 2  

T  3  U 

*"4  

->  « 

4  "  


Weight  in  Grams 


4 

20 
I20 
285 

1,220 
1,700 
2,240 

3,250 
5,620 

7,350 
8,820 
9,920 
10,720 
11,520 
12,020 
12,620 
14,820 
16,320 


Absolute 
Increment 


16 

100 

165 

350 

585 

480 

540 

1,010 

2,370 

1,730 

1,470 

1,100 

800 

800 

500 

600 

2,200 


',3 


00 


Percentage 
Increment 


400 
500 

1375 
123 

92 

39 

32 

45 

73 

31 

20 

12. 5 

8 

7-5 

4-3 

5 

14-5 

II. 3 


An  example  from  among  the  data  used  by  Ostwald  will  make  the 
matter  clear.  Table  XIII  gives  in  the  second  column  the  weights 
in  grams  of  the  human  embryo  at  monthly  inter\-als  from  the 
second  month  to  birth,  as  determined  by  Fehling,  and  of  the  child 
after  birth  at  intervals  of  three  months  during  the  first  two  years 
and  of  one  year  each  during  the  third  and  fourth  years,  as  deter- 
mined by  Camerer.    'The  third  column  of  the  table  gives  the  absolute 


450  SENESCENCE  AND  REJUVENESCENCE 

increments  in  grams  for  each  period  as  determined  from  the  differ- 
ences in  weight,  and  the  fourth  column  the  percentage  increments, 
i.e.,  the  increments  expressed  as  percentages  of  the  total  weight  at 
the  beginning  of  each  interval.  It  is  evident  at  once  that  the 
absolute  increments  in  the  third  column  increase  during  the  first 
seven  months  of  the  embryonic  period,  and  that  after  birth  there 
is  at  first  an  increase  and  then  a  decrease,  with  slight  irregularities. 
But  the  percentage  increments  show  an  increase  only  from  the 
third  to  the  fourth  month  and  afterward  a  decrease.  In  comparing 
the  increments  before  and  after  birth  it  must  be  remembered  that 
the  time  intervals  from  birth  to  two  years  are  three  times  and  those 
from  two  to  four  years  twelve  times  as  long  as  those  before  birth, 
so  that  we  must  divide  the  increments  given  in  the  table  for  these 
periods  by  three  and  by  twelve  respectively  to  make  them  com- 
parable to  the  increments  for  the  embryonic  period. 

If  from  the  growth-increments  we  plot  a  curve  of  growth,  using 
the  time  intervals  as  abcissae  and  the  increments  as  ordinates,  the 
form  and  direction  of  the  curve  will  be  very  different,  according 
as  we  use  the  absolute  or  the  percentage  increments.  The  curve 
which  results  when  the  absolute  increments  are  used  is  shown  in 
Fig.  199.  This  is  an  S-shaped  curve  and  is  similar  to  the  curve  of 
an  autocatalytic  chemical  reaction.  Ostwald  and  Robertson  have 
used  the  absolute  increments  in  their  studies  of  growth  and  have 
obtained  similar  curves  for  a  variety  of  data. 

But  if  we  use  the  percentage  increments  the  curve  is  of  the  kind 
shown  in  Figs.  200  and  201.  Fig.  200  is  the  curve  for  the  embry- 
onic period  and  Fig.  201  for  the  period  after  birth,  the  former  being 
on  a  larger  scale  than  the  latter  in  order  to  show  its  character 
more  clearly.  This  method  of  graphic  presentation  of  the  data 
gives  a  descending  curve,  which  expresses  the  fact  that  the  rate  of 
increase  in  weight  as  a  percentage  of  total  weight  decreases  from  a 
very  early  period  on.  The  other  data  of  growth  used  by  Ostwald 
and  Robertson  give  essentially  similar  results,  with  here  and  there 
shght  irregularities  resulting  from  larval  moultings,  changes  in 
relation  to  environment,  etc.  Donaldson's  and  Minot's  curves  of 
rate  of  growth  were  also  drawn  from  percentage  in  crements.^ 

'  See  Donaldson,  '95;   Minot,  '91,  '08;   and  also  pp.  274-77  above. 


I 


SOME  CURRENT  THEORIES 


451 


Per  cent 
500 


Evidently  there  must  be  no  conflict  between  the  conclusions 
which  we  may  draw  from  the  two  kinds  of  increments  or  the  two 
kinds  of  curves,  since  both  are  obtained  from  the  same  statistics. 

In  the  one  case  growth 
resembles  an  autocata- 
lytic  reaction,  in  which 
the  amount  of  substance 
added  in  a  given  lime 
increases  up  to  a  certain 
point  and  then  de- 
creases, while  in  the 
other  we  observe  that 
the  rate  of  growth,  or, 
in  other  words,  the 
growth  activity  per  unit 
of  weight,  decreases 
from  a  very  early  period 
on.  A.  W.  Meyer  ('14) 
has    criticized    Ostwald 


400 


300  - 


200  ■ 


100  ■  • 


and  Robertson  for  using 


Months  I  2345O7S9 

Fig.  200. — Cun^e  of  human  growth  for  the  embryonic  pcrio<1  and  the  month  of 
birth,  drawn  from  the  percentage  increments  of  weight  in  Table  XIII:  each  vertical 
interval  indicated  on  the  axis  of  ordinatcs  represents  an  increment  of  loo  jkt  cent  in 
weight,  and  each  horizontal  interval  on  the  axis  of  abscissae,  one  month. 


absolute  instead  of  percentage  increments  of  growth  as  the  basis 
of  their  curves.  This  criticism  is  somewhat  beside  the  point,  for  it 
must  be  remembered  that  the  absolute  and  relative  increments 
represent  simply  different  aspects  of  the  same  i>rocess. 


452 


SENESCENCE  AND  REJUVENESCENCE 


The  general  resemblance  of  the  growth  process  to  an  autocata- 
lytic  reaction  is  self-evident:  in  the  first  place  one  result  of  growth 

is  an  increase  in  the  amount  of  protoplasm, 
and  the  greater  the  amount  of  protoplasm 
the  greater  the  amount  of  growth  in  a  given 
time.  Or  more  specifically,  assuming  what 
is  undoubtedly  true,  that  growth  is  dependent 
directly  or  indirectly  upon  the  presence  of 
certain  enzymes,  then  it  is  evident  that 
greater  amounts  of  growth  are  possible  as 
growth  proceeds,  for  the  necessary  enzymes 
are  one  of  the  products  of  growth. 

Doubtless  certain  reactions  concerned  in 
growth  are  autocatalytic  reactions,  but  it 
seems  obvious  that  growth  is  very  much  more 
than  an  autocatalytic  reaction  and  that 
certain  processes  which  do  not  follow  the 
laws  of  autocatalysis  are  much  more  impor- 
tant in  relation  to  the  more  conspicuous 
characteristics  of  growth  than  those  which 
do  or  seem  to.  Growth  produces  other  sub- 
stances besides  active  protoplasm  or  enzymes, 
viz.,  substances  which  play  little  or  no  part 
in  bringing  about  further  growth,  but  form 


Years  i  2  3 

Fig.  201.— Curve  of  human  growth  from  birth  to  three  years,  drawn  from  the 
percentage  increments  of  weight  in  Table  XIII:  each  vertical  interval  indicated  on 
the  axis  of  ordinates  indicates  an  increment  of  10  per  cent  in  weight,  each  horizontal 
interval  on  the  axis  of  abscissae,  three  months. 


more    or    less    stable    structural    constituents    of    the   organism. 
As  growth  proceeds,  the  proportion  of  these  substances  to  the  total 


SOME  CURRENT  THEORIES  453 

weight  or  volume  undergoes  more  or  less  continuous  increase  and 
the  proportion  of  active  substance  to  total  weight  or  volume  becomes 
less  and  less.  Consequently  the  percentage  increment  of  growth 
decreases  more  or  less  continuously  from  the  beginning  of  these 
changes,  and  the  absolute  increment,  while  at  first  increasing,  must 
sooner  or  later  decrease.  It  is,  in  fact,  not  the  increase  in  the 
autocatalyst  of  growth,  but  the  increase  of  other  products  of  reac- 
tion and  the  transformation  of  active  protoplasm  into  other  less 
active  forms  which  retards  growth,  and  these  changes  are  going  on 
and  the  proportion  of  these  substances  is  increasing  more  or  less 
continuously  from  the  beginning  of  the  growth  period.  Enriques 
('09),  in  a  critique  of  the  autocatalytic  theory  of  growth,  has 
emphasized  the  fact  that  in  consequence  of  differentiation  a  ''dilu- 
tion" of  the  actively  growing  substance  occurs  and  the  rate  of 
growth  decreases,  until  finally  the  total  growth  is  insufficient  to 
balance  the  losses,  and  senile  atrophy  occurs.  Senescence,  senile 
atrophy,  and  death  result  from  changes  of  this  kind,  not  from  the 
autocatalytic  changes,  and  there  is  no  need  of  assuming,  as  the 
adherents  of  the  autocatalytic  theory  of  growth  are  forced  to  do, 
that  the  conditions  which  determine  senile  atrophy  are  different 
from  those  which  are  concerned  in  growth.  Senile  atrophy  is  in 
reality  merely  the  necessary  result  of  continued  growth  in  organisms 
with  a  relatively  stable  substratum. 

Growth  is  not  a  simple  chemical  reaction  and  cannot  be  con- 
sidered as  such :  it  is  a  complex  physico-chemical  process  in  which 
changes  in  the  physical  character  of  the  substratum  as  well  as 
chemical  conditions  are  concerned.  The  rate  of  growth  is  deter- 
mined, not  simply  by  the  laws  of  autocatalysis,  but  by  a  comple.x 
of  factors  of  different  kinds.  The  decrease  in  the  absolute  growth- 
increment  in  later  stages  does  not  represent  approach  toward  a 
chemical  equilibrium,  but  rather  a  continued  dilution  and  physical 
change  of  the  protoplasm. 

The  question  whether  reduction  and  dedifferentiation  are 
reversals  in  the  chemical  sense  of  growth  and  differentiatit)n  has 
already  been  raised  (see  pp.  38,  56).  If  it  were  possible  to  regard 
the  whole  life  cycle  of  the  organism  as  a  reversible  chemical  reac- 
tion it  would  doubtless  simplify  ver>'  greatly  our  conception  of 


454  SENESCENCE  AND  REJUVENESCENCE 

living  things.  But  the  organism  cannot  be  compared  to  a  chemical 
reaction;  it  consists  of  a  multitude  of  chemical  reactions  and 
physical  changes  interrelated  and  localized  and  controlled  by  their 
relations  to  a  pecuHar  physical  environment  or  substratum,  which 
in  turn  is  the  product  of  the  reactions  and  is  modified  by  them. 
Many  factors  not  concerned  in  simple  chemical  reactions  in  vitro 
are  present  in  living  organisms,  and  to  ignore  them  can  only  result 
in  failure  to  gain  an  adequate  conception  of  what  hfe  is. 

Recently  Robertson  ('13)  has  attempted  to  develop  the  auto- 
catalytic  theory  of  growth  still  farther  and  to  show  that  lecithin,  or 
the  substances  of  the  phospholipine  group  to  which  lecithin  belongs, 
are  the  autocatalysts  of  growth.  Robertson  points  out  that  two 
kinds  of  autocatalytic  growth  are  possible,  one  the  autostatic  in 
which  the  autocatalyst  is  decreasing  in  amount,  the  other  the  auto- 
kinetic  in  which  it  is  increasing  in  amount.  He  beheves  that  the 
early  period  of  embryonic  development  in  which  the  nuclear  sub- 
stance is  increasing  and  the  yolk  decreasing  is  of  the  autostatic 
type,  while  the  later  period  of  cytoplasmic  growth  and  differentia- 
tion is  of  the  autokinetic  type.  These  two  periods  correspond 
in  general  to  the  periods  which  I  have  distinguished  as  the  periods 
of  rejuvenescence  and  senescence  in  the  hfe  cycle.  The  grounds 
for  his  conclusion  that  lecithin  is  the  autocatalyst  are:  first,  that 
the  amount  of  lecithin  in  the  sea-urchin  egg  decreases  during  early 
stages  of  development  (Robertson  and  Wasteneys,  '13);  secondly, 
that  lecithin  added  to  the  sea-water  retards,  or,  as  he  beheves,  may 
even  reverse,  the  development  of  the  sea-urchin  in  early  stages; 
thirdly,  that  lecithin  accelerates  the  growth  and  development  of 
amphibian  larvae  in  later  stages  preceding  metamorphosis. 

It  is  of  course  true  that  the  amount  of  lecithin  decreases  during 
early  embryonic  development,  for  the  yolk  is  rich  in  lecithin,  and 
during  this  period  yolk  is  the  source  of  nutrition,  and  it  is  also  true 
that  the  formation  of  nuclear  substance  undergoes  marked  accelera- 
tion at  the  same  time,  but  there  is  also  increase  in  the  volume  of 
active  cytoplasm.  In  contrast  to  the  period  of  senescence  there  is 
during  this  period  of  rejuvenescence  an  increase  in  concentration, 
so  to  speak,  of  the  active  substance  of  the  organism  at  the  expense 
of  the  yolk,  and  this  increase  in  concentration  is  continuous  through- 
out the  period,  which  is  brought  to  an  end,  not  by  the  decrease  in 


SOME  CURRENT  THEORIES  455 

lecithin,  specifically,  but  by  the  disappearance  of  the  yolk  as  a 
nutritive  supply.  If  the  organism  obtains  nutrition  from  without, 
the  formation  of  both  nuclear  substance  and  cytoplasm  may  go  on 
for  a  long  time,  but  sooner  or  later  the  gradual  ''dilution"  of  the 
protoplasm  begins  to  make  itself  felt.  It  may  be  that  the  synthesis 
of  the  nuclein  of  the  nucleus  is,  as  Loeb  has  suggested,  an  auto- 
catalytic  reaction,  but  the  important  point  is  that  any  attempt  to 
interpret  the  period  of  early  embryonic  development  as  a  whole  in 
terms  of  autocatalysis  fails  to  take  account  of  features  of  great 
biological  importance. 

As  regards  Robertson's  further  evidence,  his  experiments  on 
the  retardation  of  development  by  means  of  lecithin  must  be  pre- 
sented in  rhuch  more  complete  form  before  they  can  be  regarded 
as  convincing.  To  establish  as  a  fact  a  change  so  important  as  the 
reversal  of  embryonic  development  requires  extended  and  careful 
experimentation.  There  is  no  evidence,  from  Robertson's  descrip- 
tion, of  anything  more  than  a  toxic  effect  of  the  lecithin  preparation, 
and  for  the  present  we  can  only  regard  his  conclusion  as  based  on 
very  inadequate  evidence. 

While  the  autocatalytic  theory  of  growth  is  interesting  and 
doubtless  of  value  as  regards  certain  aspects  of  growth,  it  is  at  best 
only  a  partial  theory  and  can  never  be  applied  to  the  growth  process 
as  a  whole.  The  great  periodic  changes  in  growth  during  senescence 
and  rejuvenescence  not  only  do  not  follow  the  laws  of  autocatalytic 
reactions,  but  are  determined  by  a  complex  of  factors  of  which  some 
are  only  indirectly  connected  with  chemical  reactions  of  any  kind. 
From  the  laws  of  simple  chemical  reactions  alone  we  can  never 
hope  for  anything  more  than  partial  and  inadequate  interpretations 
of  the  complex  biological  processes,  such  as  growth  and  reduction, 
differentiation  and  dedifferentiation,  senescence  and  rejuvenescence. 

REFERENCES 

Bernstein,  J. 

1898.     "Zur  Theorie  dcs  Wachstums  und  der  Bcfruchtung."  .In/;.  /. 
Entwickclungsmecli .,  \'1I. 

Blackman,  F.  F. 

1909.     "The  Manifestations  of  the  Principles  of  Chemical  Mechanics  in 
the  Living  Plant,"  Report  of  the  jStli  Meeting  of  the  Brit.  Assoc. 

for  the  Adv.  of  Sci. 


456  SENESCENCE  AND  REJUVENESCENCE 

BlJHLER,  A. 

1904.     "Alter  und  Tod,"  Biol.  Centralbl.,  XXIV. 

BUTSCHLI,  O. 

1882.     "  Gedanken  iiber  Leben  und  Tod,"  Zool.  Anzeiger,  V. 

Child,  C.  M. 

191 1.  "A  Study  of  Senescence  and  Rejuvenescence  Based  on  Experi- 
ments with  Planarians,"  Arch.  f.  Entwickelungsmech.,  XXXI. 

1914.  "Starvation,  Rejuvenescence  and  Acclimation  in  Planaria  doroto- 
cephala,"  Arch.  f.  Entwickelungsmech.,  XXXVIII. 

Cholodkowsky,  N. 

1882.     "Tod  und  Unsterblichkeit  in  der  Tierwelt,"  Zool.  Anzeiger,  V. 

COHNHEIM,  J. 

1882.  Vorlesungen  iiber  allgemeine  Pathologie.    II.  Auflage.    Berlin. 

CONKLIN,  E.  G. 

191 2.  "Cell  Size  and  Nuclear  Size,"  Jour,  of  Exp.  Zool.,  XII. 

1913.  "The  Size  of  Organisms  and  of  Their  Constituent  Parts  in  Relation 
to  Longevity,  Senescence  and  Rejuvenescence,"  Pop.  Sci.  Monthly, 
August. 

Delage,  Y. 

1903.     U  Heredite  et  les  grandes  problemes  de  la  biologic.     Paris. 

Donaldson,  H.  H. 

1895.     The  Growth  of  the  Brain.    London. 

Enriques,  p. 

1907.  "La  morte,"  Rivista  di  Scienza.    Ann.  I. 

1909.  "Wachstum  und  seine  analytische  Darstellung,"  Biol.  Centralbl., 
XXIX. 

GOETTE,  A. 

1883.  tjber  den  UrsprungdesT odes.     Hamburg. 

Hansemann,  D.  von. 

1893.    Studien  iiber  die  Spezijitat,  den  Altruismus  und  die  Anaplasie  der 

Zellen.     Berlin. 
1909.    Descendenz  und  Pathologie.    Berlin. 
Hertwig,  R. 

1889.     "tJber  die   Kernkonjugation   der   Infusorien,"   Abhandhingen  d. 

Bayer.  Akad.  d.  Wissensch.,  II.  KL,  XVII. 
1903.     "Uber  Korrelation  von  Zell-  und  Kerngrosse  und  ihre  Bedeutung 

fiir  die  geschlechtliche  Differenzierung  und  die  Teilung  der  Zelle," 

Biol.  Centralbl.,  XXIII. 

1908.  "iiber  neue  Probleme  der  Zellenlehre,"  Arch.  /.  Zellforsch.,  I. 
Jennings,  H.  S. 

1912.  "Age,  Death  and  Conjugation  in  the  Light  of  Work  on  Lower 
Organisms,"  Pop.  Sci.  Monthly,  June. 


SOME  CURRENT  THEORIES  457 

Jennings,  H.  S. 

1913.  "The  Effect  of  Conjugation  in  Paramecium,''  Jour,  of  Exp.  Zool., 
XIV. 

JlCKELI,  C.  F. 

1902.  Die  U nvollkommcnhcit  dcs  StoJJwcchscls.     Berlin. 

Kassowitz,  M. 

1899.     Allgemeine  Biologie.     Biinde  I  und  II.     Wicn. 

LOEB,  J. 

1906.  "Weitere  Beobachtungen  iiber  den  Einfluss  der  Befruchtung  und 
der  Zahl  der  Zellkerne  auf  die  Saurebildung  im  Ei,"  Biochcm. 
Zeitschr.,  II. 

1908.  "liber  den  chemischen  Character  des  Befruchtungsvorgangs  und 
seine  Bedeutung  fur  die  Theorie  der  Lebenserschcinungen,"  Vorlr. 
u.  Aufs.  a.  Entwickclimgsmech. ,  H.  II. 

1909.  Die  chemische  Enlwicklungserregung  dcs  tierischen  Eies.     Berlin. 

LoTZE,  R.  H. 

1 85 1.     Allgemeine  Physiologic  des  korpcrlichen  Lebens.    Leipzig. 
1884.     Microcosmus.     IV.  Auflage.     Leipzig. 

Magnus-Levy,  A. 

1907.  Article  "Metabolism  in  Old  Age"  in  Metabolism  and  Practical 
Medicine:    C.  von  Noorden.     Anglo-American  issue.     Chicago. 

Maupas,  E. 

1888.  "Recherches  experimentales  sur  la  multiplication  des  infusories 
cilies,"  Arch,  de  zool.  exp.,  (2),  VI. 

1889.  "La  Rajeunissement  karyogamique  chez  les  cilies," -4rc//.  dc  zool. 
exp.,  (2),  VII. 

Metchnikoff,  E. 

1903.  The  Nature  of  Man.     English  translation.     New  York  and  London. 

1910.  The  Prolongation  of  Life.  English  translation.  New  York  and 
London. 

Meyer,  A.  W. 

1914.  "Curves  of  Prenatal  Growth  and  Autocatalysis,"  Arch.  f.  Ent- 
wickelungsmcch.,  XL. 

Minot,  C.  S. 

1891.     "Senescence  and  Rejuvenation,"  Jour,  of  Physiol.,  Xll. 

1908.  The  Problem  of  Age,  Growth  and  Death.     New  York. 
1913.     Moderne  Probleme  der  Biologie.     Jena. 

Montgomery,  T.  H.,  Jr. 

1906.  "On  Reproduction,  Animal  Life  Cycles  and  the  Biological  Unit," 
Transactions  of  the  Texas  Acad,  of  Sci.,  IX. 


458 


SENESCENCE  AND  REJUVENESCENCE 


MUHLMANN,  M. 

1900.     tJber  die  Ursache  des  Alters.     Wiesbaden. 

1910.     "Das  Altern  und  der  physiologische  Tod,"  Sammlung  anat.  u. 

physiol.  Vortrdge,  H.  XL 
1914.     "Beitriige  zur  Frage  nach  der  Ursache  des  Todes,"  Arch.  f.  Pathol. 

(Virchow),  CCXV. 

MtJLLER,  J. 

1844.     Handbuch  der  Physiologie  des  Menschen.     IV.  Auflage.     Coblenz. 

OsTWALD,  Wolfgang. 

1908.  "Die  zeitlichen  Eigenschaften  der  Entwicklungsvorgange,"  Vortr. 
u.  Aufs.  a.  Entwickelungsmech.,  H.  V. 

Robertson,  T.  B. 

1908a.  "On  the  Normal  Rate  of  Growth  of  an  Individual  and  Its  Bio- 
chemical Significance,"  Arch.  f.  Entwickelungsmech.,  XXV. 

19086.  "Further  Remarks  on  the  Normal  Rate  of  Growth  of  an  Indi- 
vidual and  Its  Biochemical  Significance,"  Arch.  f.  Entwicke- 
lungsmech., XXVI. 

1913.  "On  the  Nature  of  the  Autocatalyst  of  Growth,"  Arch.f.  Entwicke- 
lungsmech., XXXVII. 

Robertson,  T.  B.,  and  Wasteneys,  S. 

1913.  "On  the  Changes  in  Lecithin-Content  Which  Accompany  the 
Development  of  Sea-Urchin  Eggs,"  Arch.  f.  Entwickelungsmech. , 
XXXVII. 

Roux,  W. 

1881.     Der  Kampf  der  Telle  im  Organismus.     Leipzig. 

Rubner,  M. 

1909.  Kraft  und  Stof  im  Haushalte  der  Natur.    Leipzig. 


CHAPTER  XVII 

SOME  GENERAL  CONCLUSIONS  AND  THEIR  SKiXITIC ANTE  TOR 

BIOLOGICAL  PROBLEMS 

It  remains  only  to  review  briefly  in  a  connected  way  some  of  the 
more  important  conclusions  of  the  preceding  chapters  and  to  make 
a  few  further  suggestions  as  to  their  bearing  upon  certain  biological 
problems.  In  the  first  place,  a  full  consideration  of  the  facts  leads 
unmistakably  to  the  conclusion  that  the  age  cycle  is  simply  one 
aspect  of  the  developmental  cycle,  or  we  might  even  say  that  the 
developmental  cycle  is  an  aspect  of  the  age  cycle.  Senescence 
and  rejuvenescence  do  not  include  special  processes,  they  are 
merely  certain  aspects  of  the  relations  between  the  metabolic  reac- 
tions and  the  protoplasmic  substratum.  The  progressive  changes 
with  which  physiological  senescence  is  associated  are  changes  in 
the  direction  of  greater  physiological  stabiHty  of  the  protoplasm 
and  decreased  dynamic  activity.  The  regressive  changes  which 
bring  about  rejuvenescence  are  not  necessarily  reversals  in  the 
chemical  sense  of  the  progressive  changes,  but  rather  a  substitution 
of  a  new  substratum  for  an  old.  As  a  structure  built  by  man.  when 
it  is  no  longer  suited  to  existing  conditions,  may  be  torn  down  and 
some  parts  of  it  used,  together  with  new  material,  for  building  a  new 
structure  which  meets  the  demands  of  the  new  conditions,  so  in 
organisms  structural  features  built  up  under  certain  physiological 
conditions  may  under  others  be  broken  down,  and  some  of  their 
constituents  may  take  part  in  the  formation  of  a  new  structure. 

Both  progression  and  regression  are  undoubtedly  going  on  at 
all  times  in  the  active  organism,  but  under  the  usual  conditions  of 
vegetative  life  the  progressive  changes  overbalance  greatly  the 
regressive  because  building  material  in  the  form  of  nutrition  is 
being  added.  But  while  growth  and  progressive  develoi)mcnt, 
with  its  specialization  and  differentiation  of  parts,  is  the  more  con- 
spicuous feature  of  the  life  cycle,  reduction  and  regression  arc  none 
the  less  essential  parts  of  it.  The  life  cycle  consists  of  one  or  more 
periods  of  senescence  and  one  or  more  periods  of  rejuvenescence. 

459 


46o  SENESCENCE  AND  REJUVENESCENCE 

When  the  organism  is  adding  to  its  structural  substance,  and  trans- 
formation from  more  active  to  less  active  physical  and  chemical 
conditions  takes  place,  senescence  occurs.  When  conditions  change 
so  that  previously  formed  structure  is  wholly  or  in  part  broken 
down  and  replaced  by  a  new  structural  substratum,  rejuvenescence 
occurs. 

Senescence  occurs  chiefly  during  the  vegetative  life  of  the  indi- 
vidual, while  rejuvenescence  is  usually  associated  with  reproduc- 
tion, although  various  other  conditions,  such  as  starvation  in  which 
extensive  breakdown  of  previously  formed  structure  occurs,  may 
bring  it  about.  Reproduction  may  be  defined  as  the  regression  or 
dedifferentiation  and  reconstitution  into  a  new  individual  of  a 
physiologically  or  physically  isolated  part  of  a  pre-existing  indi- 
vidual. In  agamic  reproduction  the  changes  result  from  the  isola- 
tion of  the  part  without  further  external  action,  but  in  gametic 
reproduction  speciaHzation  of  the  part  concerned,  i.e.,  the  gamete, 
has  proceeded  so  far  that  the  union  of  the  two  widely  different  cells 
is  necessary — except  in  parthenogenic  eggs — to  initiate  the  regres- 
sive and  reconstltutional  changes. 

The  occurrence  of  reproduction  of  one  kind  or  another  depends 
on  various  physiological  conditions,  the  degree  of  individuation, 
physiological  age,  etc.  In  general  the  vegetative  forms  of  agamic 
reproduction  occur  in  relatively  young  organisms,  the  more  spe- 
cialized agamic  reproductions,  such  as  formation  of  spores,  gem- 
mules,  etc.,  are  characteristic  of  somewhat  later  stages  with  a 
lower  metaboUc  rate,  and  finally  gametic  reproduction  is  a  feature 
of  relatively  advanced  age  and  the  gametes  are  cells  which  have 
reached  the  end  of  their  progressive  developmental  history,  have 
no  further  function  in  the  parent  organism,  and  are  cast  off  as 
waste  products  or  remain  as  physiologically  isolated  quiescent  cells. 
Before  their  isolation  they  were  integral  physiological  parts  of  the 
organism,  and  they  represent  a  more  highly  specialized,  physio- 
logically older  condition  than  those  parts  which  when  isolated 
develop  agamically. 

The  degree  of  physiological  integration  or  individuation  in- 
creases in  general  and  up  to  a  certain  limit  with  increasing  stability 
of  the  structural  substratum.     In  general,  also,  the  greater  the 


SOME  GENERAL  CONCLUSIONS  461 

degree  of  physiological  integration,  the  more  continuous  the  prog- 
ress of  senescence  and  the  less  frequently  does  vegetative  agamic 
reproduction  occur.  In  the  plants  and  lower  animals  conditions 
which  decrease  physiological  dominance  and  integration  bring 
about  reproduction  of  one  kind  or  another.  Senescence  is  itself 
such  a  condition,  and  in  many  organisms  senescence  mav  result 
automatically  in  the  physiological  isolation  of  parts,  or  the  disinte- 
gration of  the  individual  into  fragments  or  cells,  and  so  in  repro- 
duction. 

Senescence  is  a  characteristic  and  necessary  feature  of  life  and 
occurs  in  all  organisms,  but  in  many  of  the  lower  forms  it  may  be 
more  or  less  completely  balanced  by  rejuvenescence  in  connection 
with  reproduction  or  other  regressive  changes,  so  that  there  is 
little  or  no  progressive  senescence  from  one  generation  to  another, 
or  in  the  case  of  colonial  forms,  such  as  multiaxial  plants,  of  the 
colony  as  a  whole.  Life  in  such  cases  consists  of  brief  alternating 
periods  of  progression  and  regression,  of  senescence  and  rejuvenes- 
cence, which  in  some  cases  apparently  balance  each  other  for  an 
indefinite  period,  while  in  other  cases  a  slow  progressive  senescence 
may  occur,  extending  through  many  generations. 

Death  is  the  inevitable  end  of  the  process  of  senescence  when 
regression  and  rejuvenescence  do  not  occur.  In  the  lower  forms, 
where  agamic  reproduction  is  frequent,  or  where  other  conditions, 
such  as  starvation,  bring  about  regression  periodically  or  occasion- 
ally, death  does  not  necessarily  occur.  But  in  the  higher  forms, 
where  progression  and  senescence  are  more  nearly  continuous,  the 
life  of  the  individual  usually  ends  in  death,  though  even  in  these 
forms  some  degree  of  rejuvenescence  may  occur. 

If  these  conclusions  are  correct,  agamic  and  gametic  reproduc- 
tion are  fundamentally  similar  processes,  except  for  the  fact  that  in 
gametic  reproduction  specialization  of  the  reproductive  cells  has 
proceeded  so  far  that  the  peculiar  conditions  associated  with  ferti- 
Hzation  are  necessary  for  the  initiation  of  the  process  of  regression 
and  rejuvenescence.  And  if  we  accept  this  theory  of  reproduction, 
the  Weismannian  conception  of  germ  plasm  as  a  self-peri:>ctualing 
entity,  independent  of  other  parts  of  the  organism  except  as  regards 
nutrition — in  short,  a  sort  of  parasite  upon  the  body — becomes  not 


462 


SENESCENCE  AND  REJUVENESCENCE 


only  unnecessary  but  impossible.  Germ  plasm  is  any  protoplasm 
capable,  under  the  proper  conditions,  of  undergoing  regression, 
rejuvenescence,  and  reconstitution  into  a  new  individual,  organism, 
or  part.  In  other  words,  germ  plasm  becomes  merely  an  abstract 
idea  which  connotes  the  sum-total  of  the  inherent  capacities  or 
"potencies"  with  which  a  reproductive  element  of  any  kind,  natural 
or  artificial,  agamic  or  gametic,  giving  rise  to  a  whole  or  a  part, 
enters  upon  the  developmental  process.  Germ  plasm  is  then 
merely  another  term  for  heredity.  The  process  of  inheritance  is 
concerned  in  every  case  of  reproduction,  whether  it  be  agamic  or 
gametic,  partial  or  total,  and  both  experimental  reproduction  and 
agamic  reproduction  in  nature  present  opportunities  for  the  study 
of  the  process  and  mechanism  of  inheritance,  which  have  thus  far 
been  almost  entirely  neglected,  but  which  are  not  found  in  con- 
nection with  the  much  more  highly  specialized  process  of  gametic 
reproduction.  And,  admitting  that  every  reproductive  element 
of  any  kind  is,  before  reproduction  begins,  an  integral  physiological 
part  of  an  organic  individual,  we  may  define  heredity  more  briefly 
as  the  capacity  of  a  physiologically  or  physically  isolated  part  for 
reconstitution  into  a  new  individual  or  part. 

It  does  not  by  any  means  follow  from  this  theory  of  reproduction 
and  inheritance  that  all  the  characteristics  of  the  individual  shall 
reappear  in  the  following  generation.  Many  individual  charac- 
teristics which  are  the  result  of  action  of  external  factors  or  of 
special  functional  activity  of  certain  parts — such,  for  example,  as 
calloused  areas  in  the  skin,  the  functional  hypertrophy  or  atrophy 
from  disuse  of  certain  muscles,  and  many  others — are  evidently  the 
result  of  local  quantitative  changes  in  metabolism  and  as  such 
cannot  be  expected  to  alter  at  once  the  equihbrium  of  the  whole 
protoplasmic  system  in  such  a  way  that  they  will  be  reproduced 
in  following  generations  in  the  absence  of  the  special  conditions 
which  determined  their  first  appearance.  This  is  equally  true  for 
agamic  and  for  gametic  reproduction.  Nevertheless,  since  every 
reaction  represents  to  some  extent  a  reaction  of  the  whole  organ- 
ism and  no  change  is  purely  local  or  entirely  independent  of 
other  changes,  it  is  conceivable  that  if  the  special  external  or  func- 
tional conditions  act  in  the  same  way  through  a  sufficient  number 


SOME  GENERAL  CONCLUSIONS  463 

of  generations,  they  may  in  time  bring  about  an  appreciable  lasting 
change  in  the  whole  system  of  such  a  kind  that  the  characteristics 
produced  by  them  will  become  hereditary.  And  if  the  cells  which 
give  rise  to  gametes  are  integral  parts  of  the  organism,  such  a 
change  must  sooner  or  later  affect  them  as  well  as  other  parts.  It 
is  quite  impossible  to  discuss  at  this  time  the  great  mass  of  evidence 
for  and  against  the  inheritance  of  these  so-called  acquired  charac- 
ters. In  general,  biologists  have  been  slow  to  admit  the  possibility 
of  such  inheritance,  largely  because  it  conflicts  with  the  Weisman- 
nian  theory,  but  if  we  admit  that  the  gametes  are  integral  parts  of 
the  organism,  there  is  no  theoretical  difficulty  in  the  way  of  such 
inheritance.  Whatever  the  theoretical  possibilities  may  be,  it  is  in 
my  opinion  quite  impossible  to  account  for  the  course  of  evolution 
and  particularly  for  many  so-called  adaptations  in  organisms  with- 
out the  inheritance  of  such  acquired  characters,  but  since  thousands 
or  tens  of  thousands  of  generations  may  be  necessary  in  many  cases 
for  inheritance  of  this  kind  to  become  appreciable,  it  is  not  strange 
that  experimental  evidence  upon  this  point  is  still  conflicting. 

The  morphological  paralleHsm  between  the  course  of  individual 
development  and  the  course  of  evolution  have  long  been  familiar 
to  biologists  and  have  been  the  subject  of  much  discussion  and 
speculation.  While  departures  from  this  parallelism  are  numerous 
and  often  conspicuous,  nevertheless  the  so-called  biogenetic  law 
that  embryology  repeats  phylogeny,  i.e.,  the  development  of  the 
individual  repeats  evolutionary  history,  still  remains  a  striking 
biological  fact.  Moreover,  a  physiological  parallelism  seems  to 
exist  to  some  extent.  In  the  individual  we  see  advancing  diversity 
and  specialization  of  function,  apparently  associated  with  increas- 
ing stabihty  of  the  structural  substratum,  and  in  evolution  a  similar 
series  of  changes.  The  question  at  once  arises:  Can  we  not  lind  a 
clue  in  individual  development  to  certain  factors  concerned  in 
evolution  ? 

In  earlier  chapters  I  have  attempted  to  show  that  individual 
development  and  senescence  are  associated  with  the  increase  in 
stability  of  the  substratum,  while  regression  and  reju\-encscence 
involve  a  return  to  the  original  ''undifferentiated"  active  proto- 
plasmic condition.     It  is  of  course  not  necessar}'  to  assume  that  in 


464  SENESCENCE  AND  REJUVENESCENCE 

all  cases  exactly  the  same  condition  is  attained  in  each  successive 
regression  and  rejuvenescence.  It  is  quite  conceivable,  indeed 
probable,  that,  in  spite  of  the  successive  regressive  changes  in  each 
generation,  there  may  be  some  slight,  more  or  less  continuous,  pro- 
gressive change,  which  perhaps  becomes  appreciable  only  after 
many  generations.  Have  we,  in  fact,  any  right  to  assume  that 
the  organism  returns  to  exactly  the  same  condition  in  each  succes- 
sive regression?  Is  it  not  probable  that  a  gradual,  progressive 
senescence  of  protoplasm  has  occurred  in  the  course  of  evolution  ? 
These  questions  have  already  been  touched  upon  in  chap,  viii,  and 
here  it  need  only  be  said  that  the  facts  point  very  definitely  in  the 
direction  of  an  affirmative  answer. 

If  protoplasmic  senescence  is  the  essential  factor  in  progressive 
evolution,  then  evolution  is,  hke  individual  development,  to  a 
large  extent  internally,  rather  than  externally,  determined.  We 
can  accelerate,  retard,  or  alter  the  course  of  individual  development 
experimentally,  but  in  spite  of  all  such  changes  it  retains  a  remark- 
able constancy  of  character.  Have  we  not  in  evolution  a  somewhat 
similar  process,  a  progressive  change,  a  secular  differentiation  and 
senescence  of  protoplasm  along  Hues  which  are  determined  primarily 
by  the  constitution  of  protoplasm  rather  than  by  external  factors  ? 
In  our  attempts  to  modify  experimentally  the  course  of  evolution 
are  we  not  merely  bringing  about  minor  changes  in  a  process 
which,  like  individual  development,  is  internally  determined,  rather 
than  determining  the  essential  factors  in  evolution?  Here  again 
the  facts  seem  to  suggest  an  affirmative  answer. 

If  evolution  is  in  some  degree  a  secular  differentiation  and 
senescence  of  protoplasm,  the  possibility  of  evolutionary  rejuvenes- 
cence must  not  be  overlooked.  Perhaps  the  relatively  rapid  rise  and 
increase  of  certain  forms  here  and  there  in  the  course  of  evolution 
may  be  the  expression  of  changes  of  this  sort.  Perhaps  also  those 
forms  which  have  been,  so  to  speak,  left  behind  as  the  lower  organ- 
isms in  evolutionary  progress  are  forms  in  which  senescence 
and  rejuvenescence  more  nearly  balance  than  in  those  that  have 
gone  on. 

Even  if  evolution  is  a  process  of  this  kind  we  must  beheve  that 
environmental  factors  affect  its  course  to  a  greater  or  less  extent, 


SOME  GENERAL  CONCLUSIONS  465 

as  they  do  the  course  of  individual  development,  and  we  must  admit 
the  possibility  of  sudden  changes  of  considerable  magnitude,  so- 
called  mutations,  although  even  these  may  be  determined  by  pre- 
viously existing  internal  conditions,  as,  for  example,  metamorjihosis 
in  individual  development  which  is  primarily  the  result  of  internal 
factors.     And,  finally,  as  our  ability  to  control  the  process  of  indi- 
vidual development  has  increased  so  greatly  with  the  advance  in 
knowledge  of  experimental  methods,  we  may  perhaps  expect  that 
in  the  course  of  time  our  ability  to  control  the  evolutionary  pro- 
cess may  increase,  although  the  difficulties  involved  in  controlling 
and  modifying  to  any  very  great  degree  internal  conditions  which 
are  the  result  of  milHons  of  years  of  alternating  progressive  and 
regressive  change  will  perhaps  make  progress  in  this  direction  slow. 
Senescence  and  rejuvenescence  result  from  a  combination  of 
factors  which  is  found  nowhere  except  in  organisms,  but  there  is  no 
reason  to  believe  that  any  one  of  the  factors  which  make  up  the 
complex  is  peculiar  to  living  things.     Changes  in  the  permeability 
of  membranes  and  other  changes  in  aggregate  condition  of  the 
colloids,  changes  in  proportion  of  active  and  inactive  substance  in 
chemical  systems,  changes  in  water-content — all  these  and  many 
others  occur  in  non-living  as  well  as  in  living  systems.     But  we 
may  make  our  basis  of  comparison  broader  than  this  and  use  for 
definitions  somewhat  more  general  terms  than  heretofore.     In  such 
terms  senescence  is  a  retardation  resulting  from  continued  dynamic 
activity  under  certain  conditions  in  a  system,  and  rejuvenescence 
an    acceleration    resulting    from    elimination    or    transformation 
of  the  retarding  factors  under  altered  conditions.     These  delini- 
tions  still  hold  good  for  the  organism,  but  they  also  apply  to  many 
other  changes  in  nature.     Senescence  and  rejuvenescence  in  this 
sense  are  going  on  all  about  us,  in  some  cases  with  short,  in  others 
with  very  long,  periods.     The  age  changes  in   the  organism  are 
merely  one  aspect  of  IVerden  iind    Vergchcn,   the   becoming   and 
passing  away,  which  make  up  the  history  of  the  universe. 


D.  H.  HILL  LIBRARY 
North  Carolina  State  Coileg* 


I 


INDEX 


INDEX 


Note. — References  give  the  number  of  the  page  on  which  the  matter  referred  to  begins. 


Acclimation:  in  relation  to  concentra- 
tion of  reagent,  72;  in  relation  to  age, 
82;  in  relation  to  temperature,  84; 
in  relation  to  nutrition,  84, 165;  in  rela- 
tion to  metabolic  rate,  164.  See  also 
Susceptibility. 

Age:  physiological  and  morphological, 
58,  85;  criteria  of,  85,  178;  in  relation 
to  time,  87,  97;  in  relation  to  hydranth 
and  medusa  buds  in  Pennaria,  151, 
256;  in  relation  to  vegetative  repro- 
duction in  plants,  239;  in  relation  to 
spore  formation  in  plants,  247;  of 
gametes,  349;  in  relation  to  matura- 
tion, 355;  in  relation  to  gamete  forma- 
tion, chap,  xiv;  in  relation  to  partheno- 
genesis and  zygogenesis,  393.  See 
also  Age  cycle;  Rejuvenescence; 
Senescence. 

Age  cycle:  occurrence  of,  59;  in  relation 
to  endomi.xis,  143,  379;  in  relation  to 
character  of  nutrition,  169,  179;  in 
relation  to  reproduction,  178,  239,  247; 
in  relation  to  other  periodicities,  187, 
192;  in  relation  to  spore  formation, 
254;  individual  and  racial,  in  relation 
to  parthenogenesis  and  zygogenesis, 
389;  in  relation  to  larval  stages  and 
metamorphosis,  420;  as  one  aspect  of 
developmental  cycle  in  world  in  gen- 
eral, 465.  See  also  Age;  Life  cycle; 
Rejuvenescence;   Senescence. 

Alternation  of  generations:  in  relation 
to  age  cycle  in  plants,  253;  in  mosses 
and  ferns,  254,  366;  in  seed  plants,  254, 
320,  368. 

Anabolism,  14,  43. 

Anophthalmic  form  in  Planaria  dorolo- 
cephala,  112,  223. 

Antheridium:  in  algae,  316;  in  mosses 
and  ferns,  318. 

Apical  region:  metabolic  rate  in,  202, 
204;  independence  of,  210,  213,  215; 
dominance  of,  213,  215,  216;  limit  of 
dominance  in,  among  plants,  232,  238; 
physiological  condition  of,  in  plants, 
240,  244.  See  also  Axial  gradient; 
Axis. 

Aplysia  limaclna,  oxygen  consumption 
and  carbon-dioxide  production  during 
early  development  in,  411. 


Apogamy:  origin  of  embryo  in,  322;  in 
relation  to  segregation  of  germ  plasm, 
367;   in  seed  plants,  40S. 

Apospory,  322  footnote  2,  408. 

Arbacia  pitiictiilala:  increase  in  oxygen 
consumption  of,  after  fertilization, 
405;  increase  in  susce[)tibilily  of, 
during  early  development,  413,  414. 
See  also  Sea-urchin. 

Archegonium:  of  mosses,  316;  of  fern, 
338;  of  Torre  ya  taxi  folia,  339. 

Arenicola  crislata:  period  of  devclo|)men- 
tal  rejuvenescence  in,  compared  with 
that  of  Xereis,  415. 

Arteriosclerosis  in  relation  to  senescence, 
287,  301,  434. 

Ascaris  megalocephala:  germ  path  in, 
324;  spermatozoon  of,  336;  suscepti- 
bility of  gametes  of,  351. 

Asterias  forbesii,  susceptibility  of,  during 
early  development,  413.  See  also 
Starfish. 

Atrophy:  senile,  2,  287,  301;  from  dis- 
use, 45,  185,  287;  difference  between, 
and  reduction,  288;  of  sex  organs  as 
condition  of  senescence,  434. 

Autocatalyst,  lecithin  as,  of  growth,  454. 
See    also     .\utocatalytic  reaction. 

Autocatalytic  reaction:  growth  as,  446, 
452;  nature  of,  44();  curve  of,  446; 
autostatic  and  autokinelic.  454;  leci- 
thin in,  of  growth,  454. 

Axial  gradient:  in  Planaria  dorolocephaJa, 
122,  202;  in  Sleiiosloniuni,  135;  in 
other  forms,  203;  along  polar  axis. 
202,  243;  along  axis  of  symmetry,  203; 
changes  in,  during  development,  203, 
207;  in  rate  of  growth,  204;  in  animal 
mori)hogenesis,  204;  origin  of.  207; 
persistence  of.  through  reproduction, 
209;  establishment  of,  200;  in  relation 
to  organic  axes,  200;  as  basis  of  indi- 
viduation, 225;  maintenance  of,  2  2(>; 
of  eggs  in  relation  to  larval  develop- 
ment, 420;  change  in,  during  lar\al 
development  of  .Wreis.  421.  Srr  also 
Dominance;  Individual;  Individua- 
tion. 

Axiate.  See  .\xis.  Individual,  Individua- 
tion. 


469 


470 


SENESCENCE  AND  REJUVENESCENCE 


Axis,  organic:  presence  of,  200,  203;  of 
polarity  and  symmetry,  200,  201,  203; 
as  metabolic  gradient,  209,  225.  See 
also  Axial  gradient. 

Axolotl,  389. 

Banana,  vegetative  propogation  of,  239, 
370- 

Bee,  parthenogenesis  in,  345,  395. 

Begonia:  dedifferentiation  in,  246;  con- 
trol of  flowering  in,  376. 

Biaxial  forms:  in  Tubidaria,  210;  in 
Planaria  dorotocephala,  213;  in  Plana- 
ria  simpUcissima,  215. 

Biogene  hypothesis,  15. 

Biogenetic  law,  significance  of,  463. 

Biometer,  73,  156,  160,  202. 

Branchipus:  conditions  of  hatching  in, 
404;    larval  metamorphosis  in,  422. 

Budding:  in  hydra,  145;  in  Pennaria, 
147,  150;  in  plants,  231,  239;  adven- 
titious, in  plants,  229,  246. 

Carbon-dioxide  production:  decrease  of, 
in  narcosis,  71;  estimation  of,  73,  202; 
during  starvation  in  Planaria  doro- 
tocephala, 161;  decrease  of  metabolic 
rate  by,  188;  in  nervous  system  of 
Limulus,  273;  in  early  development  of 
Aplysia  limacina,  411.  See  also  Meta- 
bolic rate;  Oxidation;  Oxygen  con- 
sumption. 

Cassiopea,  reduction  of,  during  starva- 
tion, 163. 

Catalysis:  role  of  colloids  in,  25;  retar- 
dation of,  67,  184;  by  products  of 
reaction,  446.  See  also  Autocatalytic 
reaction. 

Cell:  embryonic  or  undifferentiated,  48, 
5 1 ,  242 ;  differentiation  and  dedifferenti- 
ation of,  52,  57,  239,  245,  257,  286,  294; 
metabolic  conditions  in,  39,  51,  183; 
relation  of,  to  life,  41;  division  of,  in 
infusoria,  137;  in  starvation,  155; 
cyclical  changes  in,  189,  297;  axes  of, 
200;  plant  spore  as  specialized,  247, 
253;  nucleoplasmic  relation  in,  284, 
285,  418,  439,  440;  length  of  life  of, 
307;  origin  of  gametic,  in  plants,  316; 
differentiation  of  gametic,  in  plants, 
316,  334,  337;.  origin  of  gametic,  in 
animals,  323 :  differentiation  of  gametic 
in  animals,  334, 339.  See  also  Dediffer- 
entiation; Differentiation;  Gamete  for- 
mation; Gametes;  Infusoria;  Nervous 
system. 

Chaetoplerus  pergamenlaceus:  axial  gradi- 
ent in  embryo  of,  203;  susceptibility  in 


eggs  of,  after  fertilization,  406;    reju- 
venescence during  early  development 

of,  415- 

Cliara,  gametes  of,  316. 

Chironomus,  germ  path  of,  328. 

Chromatin,  diminution  of,  324,  328. 

Chromosomes,  haploid  and  diploid  num- 
ber of,  322  footnote  2,  353. 

Chrysanthemum,  dedifferentiation  in,  246. 

Clavellina,  dedifferentiation  in,  258. 

Colloids:  characteristics  of,  21;  suspen- 
soid,  21;  emulsoid,  21;  significance  of, 
for  morphogenesis,  22;  role  of,  in  life  in 
general,  22,  26;  in  relation  to  water  and 
salts,  24;  membranes  composed  of,  24; 
as  catalyzers,  25;  role  of,  in  transmis- 
sion, 26;  in  relation  to  substratum,  41; 
in  relation  to  differentiation,  48 ;  coagu- 
lation of,  in  relation  to  temperature,  49 ; 
changes  of,  with  time,  50,  184.  See 
also  Proteids;   Substratum. 

Colony:  in  Pennaria,  148;  in  plants, 
237,  369- 

Colpidium:  rejuvenescence  of,  in  agamic 
reproduction,  141;  susceptibility  of,  at 
time  of  conjugation,  352,  381;  effect 
of  prevention  of  agamic  reproduction 
on,  380. 

Conducting  paths:  in  relation  to  physio- 
logical correlation,  217,  260;  in  ani- 
mals, 218,  224,  268;  in  plants,  238; 
See  also  Conductivity;  Dominance, 
Transmission. 

Conductivity,  217,  218,  227,  232,  260, 
268.  See  also  Dominance;  Trans- 
mission. 

Conjugation:  Maupas'  conclusions  con- 
cerning, 64,  377,  434;  breeding  with- 
out, in  Paramecium,  136,  377;  experi- 
mental determination  of,  378;  in 
relation  to  endomixis,  379,  380;  capa- 
city of  different  races  for,  381 ;  effect  of, 
404.     See  also  Fertilization. 

Correlation,  phj'siological:  mechanical, 
217;  chemical,  217,  224;  transmissive, 
217;  increase  in  complexity  of,  in 
higher  animals,  266.  Sec  also  Domi- 
nance; Individual;  Individuation; 
Isolation. 

Correlative  differentiation,  50.  See  also 
Differentiation. 

Corymorpha  pal  ma:  susceptibility  in 
relation  to  age  of,  loi;  rejuvenescence 
in  reconstitution  of,  no. 

Crepidula,  nucleoplasmic  relation  in,  419. 

439- 
Cyclops,  germ  path  in,  327.  , 

Cymatogaster,  germ  path  in,  330. 
Cytomorphosis,  284,  440. 


INDEX 


471 


Daphnid  Crustacea,  parthenogenesis  and 
zygogenesis  in,  389. 

Death:  absence  of,  i,  260,  303;  chemical 
conceptions  of,  15,  306;  disintegration 
as  criterion  of,  in  lower  animals,  74; 
from  starvation,  156,  298,  302;  in  re- 
lation to  character  of  nutrition  in 
Planar ia  velata,  170,  174;  of  parts  in 
plants,  239,  241;  of  cells  in  animals, 
257;  necessity  of,  in  higher  animals, 
270;  conditions  of,  in  higher  animals, 
301 ;  physiological  or  natural,  301 ,  309; 
various  views  concerning,  301,  304, 
306,  307,  308,  chap,  xvi;  in  relation 
to  nervous  system,  301,  307;  from 
exhaustion  in  animals,  302;  appearance 
of,  in  evolution,  304;  in  unfertilized 
starfish  egg,  307,  405;  temperature 
coefficient  of,  in  sea-urchin  larvae, 
308,  of  flower  in  plants,  368;  from  old 
age  in  infusoria,  382;  after  experi- 
mental treatment  of  eggs,  409;  at 
critical  stage  of  development,  414; 
of  larval  parts,  422;  as  result  of  ex- 
haustion of  "life  ferment,"  436;  as 
result  of  differentiation,  436,  442; 
Miihlmann's  theory  of,  437;  in  relation 
to  autocatalytic  theory  of  growth,  448; 
as  end  of  senescence,  461.  See  also 
Age;  Age  cycle;  Dedififerentiation; 
Development;  Differentiation;  Re- 
juvenescence;  Senescence. 

Decrement,  in  transmission,  209,  217,  268. 
See  also  Transmission. 

Dedifferentiation :  definition  of,  54; 
process  of,  55;  conditions  of,  57; 
course  of,  58;  experimental  evidence 
for,  179,  180,  294,  295;  as  a  condition 
of  reproduction,  234;  in  vegetative 
life  of  plants,  239;  in  plant  cell,  245, 
252;  observational  evidence  for,  in 
animals,  257;  limited  capacity  for,  in 
higher  animals,  267,  286;  in  striated 
muscle,  294;  in  nerve,  295;  in  ex- 
planted  kidney  cells,  295;  after  hiber- 
nation, 296;  in  embry^os  of  starfish  and 
sea-urchin,  413;  in  early  embryonic 
development  of  animals,  418,  420;  in 
early  embryonic  development  of  plants, 
424.  See  also  Reconstitution;  Reduc- 
tion;   Rejuvenescence. 

Dendrocoeliim  lacleum,  susceptibility  of, 
in  relation  to  age,  loi. 

Development:  reversibility  of,  56,  64, 
155,  446;  progressive,  57;  regressive, 
57,  155;  in  relation  to  age  cycle,  182; 
orderly  character  of,  199;  law  of 
antero-posterior,  204;  repetition  in,  220, 
269;  continuity  of,  239,  247,  267,  270; 
temperature    coefficient    of,    308;     of 


gametes  as  process  of  specialization, 
316,  7,T,y,  stage  of,  in  relation  to 
flowering,  373;  initiation  of,  in  rela- 
tion to  fertilization,  403;  initiation  of. 
in  parthenogenesis,  406;  ex|)erimenlal 
initiation  of,  408;  experimenlal  treat - 
ment  of  eggs  in  relation  to,  409; 
critical  stages  in,  413;  increase  in  sus- 
ceptibility during  early  embryonic, 
412;  different  rate  of,  in  Taulogolabrus 
axvd  FiDidulus,  417;  nucleoplasmic 
relation  in  early  embryonic,  418;  cyto- 
plasmic changes  during  early  embry- 
onic, 419;  embryonic,  in  plants  in 
relation  to  age  cycle,  424;  Muhlmann's 
conception  of,  439;  reversal  of,  by 
lecithin,  454.  See  also  Differentiation; 
Reconstitution;    Senescence. 

Differentiation:  as  general  characteristic 
of  organisms,  i;  chemical  conception 
of,  17;  physico-chemical  conception 
of,  23;  physical  analogy  to,  28;  defini- 
tion of,  46;  quantitative  factors  of,  47; 
in  relation  to  metabolic  rate,  47,  51,  53; 
factors  of,  51;  different  degrees  of, 
53,  286;  reversibility  of,  56,  64,  155. 
446;  not  primarily  dependent  on 
chemical  correlation,  224;  quantity 
and  quality  in,  226;  in  plants,  240, 
242,  244,  245;  in  higher  animals,  267, 
286;  in  gametes  of  plants,  316,  334, 
337,  346;  in  gametes  of  animals,  334, 
339,  346;  in  relation  to  chemical  con- 
stitution of  sperm  head,  353;  of 
flower,  368,  373,  375;  in  early  embry- 
onic development,  420;  as  determin- 
ing senescence,  442;  secular,  in 
evolution,  464.  See  also  Dedifferen- 
tiation; Development;  Gametes;  Re- 
constitution;  Senescence. 

Diminution:  of  chromatin  in  Asccris 
megalocephala,  324;  dependence  of, 
on  cytoplasmic  environment,  327; 
of  chromatin  in  Miastor,  ^2$. 

Dominance,  physiological:  in  relation  to 
apico-basal  axis,  54,  213,  215,  216;  in 
relation  to  metabolic  rate,  216;  in 
relation  to  chemical  correlation,  217; 
in  relation  to  transmission,  217,  224; 
limit  of,  217,  219,  220,  223,  268-  exten- 
sion of,  during  development,  219,  231. 
232,  238,  268;  spatial  factor  of,  in  |K)si- 
tion  of  parts,  222;  nature  of.  225;  in 
embryonic  tissue  of  plants,  243.  Ser 
also  .\xial  gradient;  Individual;  Indi- 
viduation. 

Dyliscits  ?itargiiialis,  oogenesis  of,  341. 

Egg.  See  Fertilization;  damctc  forma- 
tion;    Gametes;     Tarthcnogenic    egg; 


472 


SENESCENCE  AND  REJUVENESCENCE 


Reproduction,     gametic;      Zygogenic 

Embryo  sac,  development  of,  320.  See 
also  Gametophyte. 

Encystment:  in  Planarla  velata,  131; 
in  relation  to  character  of  nutrition  in 
Planar ia  velala,  169;  in  relation  to  age 
cycle,  255,  256;  influence  of  envelope 
in,  404. 

Endomixis:  process  of,  143;  in  relation  to 
age  cycle,  143;  in  relation  to  conjuga- 
tion, 379,  380. 

Entelechy,  9,  54. 

Enzymes:  colloid  character  of,  25;  re- 
tardation of  action  of,  67,  184;  stabil- 
ity of  substratum  in  relation  to,  41. 

Epigenesis,  46. 

Equisetum,  spermatozoid  of,  334. 

Evolution:  increase  in  physiological 
stability  of  substratum  during,  45, 
53,  194,  267,  298,  304,460;  increase 
in  differentiation  during,  53,  286; 
limitation  of  dedifierentiation  during, 
57,  230,  267,  286;  increase  in  degree 
of  individuation,  during  227,  266,  304; 
senescence  and  rejuvenescence  in,  193; 
course  of,  in  plants,  241;  appearance 
of  death  during,  304;  of  length  of  life 
and  of  death,  304;  interpretation  of, 
from  individual  development,  463; 
as  a  secular  senescence  of  protoplasm, 
464;  possibility  of  control  of,  464. 

Exhaustion:  distinction  between,  and 
fatigue,  297;  distinction  between,  and 
senility,  297;  as  cause  of  death,  302. 

Fasciola  hepatica,  oogenesis  of,  340. 

Fatigue:  nature  of,  188,  297;  distinction 
between,  and  exhaustion,  297;  mental, 
297;  in  relation  to  senility  in  nerve 
cell,  297. 

Fertilization:  rejuvenescence  in  con- 
nection with,  307,  434;  prevention  of 
death  by,  307,  404;  absence  of,  in 
apogamy  in  plants,  322;  effect  of,  403, 
424;  quiescent  period  following,  403; 
metabolic  rate  in  animal  eggs  after, 
405,  413.  See  also  Conjugation; 
Gametes;  Parthenogenesis;  Partheno- 
genic  egg. 

Fission:  act  of,  in  Planaria  dorotoccphaJa, 
124;  prevention  of,  in  Planaria  dorolo- 
cephala,  125;  in  Stenostomnm,  135; 
in  infusoria,  137;  in  consequence  of 
decreased  metabolism,  232. 

Fission  plane:  in  Stenostomnm,  135;  in 
infusoria,  138. 

Flower:  rate  of  oxidation  in,  349,  374; 
definition  of,  368;  differentiation  of, 
368,  373,  375 ;   origin  of,  368;   limited 


growth  of,  368;  transformation  of, 
into  vegetative  shoot,  376.  See  also 
Flowering. 

Flowering:  in  relation  to  senescence,  368; 
early,  in  cuttings  from  blooming  plants, 
369;  influence  of  light  on,  371;  experi- 
mental control  of,  372;  physiological 
conditions  of,  373;  periodic  repetition 
of,  375;   premature,  376. 

Fragmentation:  in  Planaria  velata,  130; 
in  relation  to  character  of  nutrition, 
169;   in  relation  to  age  cycle,  255,  256, 

259- 
Functional  hj^pertrophy,  43. 

Funduhis  heteroclitus:  susceptibility  dur- 
ing early  development  of,  416;  period 
of  developmental  rejuvenescence  in, 
compared  with  that  in  Tauiogolabrus, 
417. 

Gamete  formation:  in  algae  and  fungi, 
316;  in  mosses  and  ferns,  318;  in  seed 
plants,  320,377;  as  a  process  of  special- 
ization, 322,  330;  conditions  of,  in 
lower  plants  in  relation  to  age,  364; 
conditions  of,  in  mosses  and  ferns 
in  relation  to  age,  366;  loss  of  capacity 
for,  367,  370;  conditions  of,  in  seed 
plants,  368;  conditions  of,  in  protozoa, 
377;  conditions  of,  in  hydra,  383;  con- 
ditions of,  in  margelid  medusa,  384; 
conditions  of,  in  planarians,  384; 
conditions  of,  in  parasitic  flatworms, 
387;  conditions  of,  in  other  inverte- 
brates, 388;  conditions  of,  in  verte- 
brates, 388;  premature,  389;  in 
trematode  larvae,  395.  See  also 
Gametes. 

Gametophyte:  in  relation  to  life  cycle, 
253;  in  mosses  and  ferns,  253,  366; 
development  of,  in  seed  plants,  320, 
377;   omission  of,  322,  408. 

Gametes:  ph\'siological  condition  of, 
270,  460;  morphological  condition  of, 
270,  316,  333;  theoretical  significance 
of  origin  of,  315;  of  algae  and  fungi, 
316;  of  mosses  and  ferns,  318;  in  seed 
plants,  320;  origin  of,  in  animals,  322; 
differentiation  of  parthenogenic  and 
zygogenic,  343;  metabolic  rate  in 
development  of,  349;  motor  activity 
in  male,  350;  susceptibility  of,  351; 
physiological  conditions  of  maturation 
in,  353;  different  specialization  of,  in 
infusoria,  404.  See  also  Fertiliza- 
tion; Gamete  formation;  Germ  path; 
Germ  plasm;    Reproduction,  gametic. 

Gemmules  of  sponges,  in  relation  to  age 
cycle,  256,  259. 


INDEX 


473 


Germ  path:  absence  of,  in  plants,  316; 
in  A  scar  is  mcgalocepliala,  324;  deter- 
mined by  cytoplasmic  conditions,  327, 
328,  329;  in  Cyclops,  327;  in  Sac^illa, 
327;  in  Chironomus,  328;  in  Miastor, 
328;  in  chrysomelid  beetles,  328; 
in  hymenoptcra,  329;  in  vertebrates, 
329;  absence  of,  in  certain  animals, 
331.  Sec  also  Gamete  formation, 
Gametes. 

Germ  plasm,  2,  3,  55,  64,  179,  315,  322, 
330.  332,  346,  356,  397,  461;  supple- 
mentary, 315,  333;  no  segregation  of, 
in  plants,  316;  question  of  continuity 
of,  in  plants,  323;  supposed  segregation 
of,  in  animals,  323;  not  an  independent 
entity  in  A  scar  is  mcgalocepliala,  327; 
definition  of,  462.  See  also  Gametes; 
Germ  path;   Reproduction,  gametic. 

Gliadin,  in  nutrition  experiments,  278. 

Gonophore  of  hvdroids,  dediflerentiation 
of,  258.  _ 

Growing  tip:  in  Planaria  dorotoccphala, 
124;  in  plants,  204,  216,  221,  229,  2^2, 
238,  240,  244,  246;  inhibition  of,  221, 
231. 

Growth:  as  general  characteristic  of 
organisms,  i;  chemical  conception  of, 
16,  38;  in  organism  and  in  crystal,  16; 
definitions  of,  34,  37;  changes  in  water 
content  during,  36;  reversibility  of, 
38;  different  processes  of,  38;  proteid 
synthesis  in,  39;  in  relation  to  rate  of 
oxidation,  43,  279;  rate  of,  in  relacion 
to  age,  86,  96,  240,  273,  282;  of  new 
tissue  in  reconstitution  of  Planaria 
dorotoccphala,  103;  axial  gradients  in 
rate  of,  204;  beyond  limit  of  individual 
size,  220.  229,  231;  in  relation  to 
agamic  reproduction  in  plants,  239; 
limitation  of,  by  differentiation  in 
higher  animals,  223,  230,  268;  correct 
measure  of  rate  of,  273;  periodic,  276, 
388;  difference  between,  and  mainte- 
nance, 278;  during  partial  starvation  in 
mammals,  280;  senescence  in  mammals 
without,  282;  after  starvation  in  birds 
and  mammals,  298;  after  starvation 
in  amphibia,  300;  energy  requirement 
for,  in  mammals,  305;  rate  of,  in 
gametes,  349;  in  relation  to  gamete 
formation  in  algae  and  fungi,  364; 
limitation  of,  in  flower,  368;  cessation 
of,  at  flowering,  369;  in  relation  to 
surface  and  volume,  438;  as  an  auto- 
catalytic  reaction,  446,  452;  founda- 
tion of  autocatalytic  theory  of,  448; 
significance  of  absolute  and  relative 
increments  of,  449;  inadequacy  of 
autocatalytic    theory    of,    452,    455; 


lecithin  as  autocatalyst  of,  453.  See 
also  Reduction. 
Growth  impulse:  assumption  of,  un- 
necessary, 45;  supi)osed  location  of, 
in  mammals,  280;  senescence  as  inhi- 
bition of,  434. 

Headless  form  in  Planaria  dorotoccphala, 
112. 

Heat  production :  in  relation  to  body  sur- 
face, 272;  during  early  embryonic 
development  of  sea-urchin,  412. 

Heredity:  in  relation  to  germ  plasm,  462; 
definition  of,  462. 

Heterotypic  mitosis:  in  maturation,  334; 
occurrence  and  experimental  produc- 
tion of,  in  other  cells,  334. 

Histone,  in  sperm  head,  353. 

Hordein,  in  nutrition  experiments, 
278. 

Hormones,  224.     See  also  Correlation. 

Hydra:  susceptibility  of,  in  relation  to 
age,  loi;  rejuvenescence  of,  in  recon- 
stitution, no;  budding  in,  145;  reju- 
venescence of,  in  agamic  reproduction, 
145;  oogenesis  of,  340;  conditions  of 
gamete  formation  in  383. 

Ilydroidcs  dianllius:  susceptibility  of 
eggs  of,  after  fertilization,  406;  rejuve- 
nescence during  early  development  of, 
415- 

Increment:  absolute  and  relative,  in 
growth,  273,  449;  decrease  in  relative, 
of  growth  during  senescence,  274. 

Individual,  organic:  nature  of,  54,  225; 
agamic  formation  of,  in  Planaria  doro- 
toccphala, 122;  definitions  of,  199,  225; 
characteristics  of,  199;  radiate  type  of, 
200;  axiate  type  of,  200,  225;  inade- 
quacy of  current  theories  of,  201; 
axial  gradients  in,  202;  dominance 
and  subordination  in,  210;  limit  of 
dominance  and  size  of,  217;  other 
factors  limiting  size  of,  223,  230,  26S; 
in  the  plant  body,  237.  Sec  also 
Dominance;  Individuation;  Isolation, 
physiological. 

Individuation:  in  posterior  region  of 
Planaria  dorotoccphala,  123;  dilTcrcnt 
kinds  of,  199;  nature  of,  225;  degree 
of,  227.  239,  240,  266,  304,  460;  of 
plant  as  a  whole,  237;  in  vegetative 
reproduction  in  plants.  238;  in  s|X)re- 
bearing  [larls  of  jilants,  241 ;  in  cmbn.-- 
onic  tissue  of  plants.  243;  in  jilant 
spore,  252;  in  relation  to  death,  304. 
See  also  Dominance;  Individual; 
Isolation,  physiological. 


474 


SENESCENCE  AND  REJUVENESCENCE 


Infusoria:  age  changes  in,  136;  agamic 
reproduction  in,  137;  endomixis  in, 
143;  rhythms  of  growth  and  division 
in,  143;   immortality  of,  145. 

Inhibition:  in  production  of  subnormal 
forms  in  Planaria,  113;  of  senescence, 
167,  239,  257,  27Q,  303. 

Integration,  physiological,  224,  227, 
267,  424,  460.  See  also  Dominance; 
Individuation;  Isolation,  physiologi- 
cal; Reconstitution;  Reproduction, 
agamic,  experimental. 

Intelligence:  in  construction  of  machine, 
29;  in  organism,  30;  in  relation  to 
structure,  30. 

Involution  in  Planaria  velata,  172. 

Irritability,  Winterstein's  conception  of, 
70. 

Isolation,  physiological:  m  Planaria 
dorotocephala,  124;  in  Planaria  velata, 
130;  in  Ttibularia,  220;  in  plants,  221, 
239;  as  condition  of  reproduction,  229; 
by  increase  in  size,  229,  231,  239; 
by  decrease  of  dominance,  229,  231; 
effect  of,  230,  239;  by  decrease  in  con- 
ductivity, 232;  by  direct  action  of 
external  factors,  232;  infrequency 
of,  in  higher  animals,  268;  in  partheno- 
genesis, 406;  in  segmentation  of  Nereis 
larva,  422.  See  also  Dominance; 
Individual;   Individuation. 

Katabolism:  14,  43>  278. 

Lability,   14,   17,    18,    19.   38-     See  also 

Stability,  physiological;   Substratum. 
Larva:    of  trematodes,  395:    of  Nereis, 

414,     421;      characteristics    of,     420; 

metamorphosis  of,  420;    segmentation 

in,  421. 
Lecithin:     as    autocatalyst    of    growth, 

454;   reversal  of  development  by,  454; 

disappearance  of,  in  early  development, 

454- 
Life:  neo-vitalistic  conception  of,  9; 
chemical  conception  of,  15;  physico- 
chemical  conception  of ,  19,  26;  relation 
to  colloids,  22,  26;  substratum  and 
reactions  both  necessary  for,  26;  be- 
ginning of,  26;  indissociability  of 
structure  and  function  in,  28;  relation 
of  intelligence  to,  30,  31;  Huxley's 
conception  of,  41;  cyclical  character 
of,  59;  temperature  coefficient  of 
length  of,  68,  308;  without  gametic 
reproduction,  99,  130,  136,  239,  366 
369,  386,  387,  3S8;  length  of,  in  higher 
animals,  301;  factors  in  length  of,  302; 
relation  of  length  of,  to  time,  303; 
theories  of  length  of,  304-    See  also  Age; 


Age  cycle;  Death;  Dedifferentiation; 
Differentiation;  Life  cycle;  Rejuvenes- 
cence; Senescence,  individual,  racial, 
evolutionary. 

Life  cycle:  occurrence  of,  59;  in  rela- 
tion to  age  cycle,  182;  of  plants,  252, 
254,  365,  369;  of  infusoria,  382;,  of 
daphnid  Crustacea,  389;  of  rotifers, 
392;  of  digenetic  trematodes,  395. 
See  also  Life. 

Limuhis  polyphemits:  in  relation  to  evolu- 
tionary senescence,  193;  carbon-dioxide 
production  in  nervous  system  of,  273. 

Lingula,  in  relation  to  evolutionary 
senescence,  193. 

Lipoids:  in  membranes,  25;  role  of,  in 
narcotic  action,  69,  75;  increase  of,  in 
animal  oogenesis,  353. 

Lumbriculiis,  rejuvenescence  of,  in  recon- 
stitution, no. 

Maintenance:  difference  between,  and 
growth,  278;  energy  requirement  for, 
in  mammals,  306. 

Maturation:  as  a  cause  of  death,  307, 
309;  in  relation  to  life  cycle  in  plants 
and  animals,  324;  cytology  of,  353; 
heterotypic  division  in,  354;  physio- 
logical interpretation  of,  355,  356;  con- 
ditions of,  in  animal  egg,  355;  in  germ 
cells  of  trematode  larvae,  395;  differ- 
ent conditions  of,  in  sea-urchin  and 
starfish,  405;  increase  of  oxidation 
during,  405,  406,  413;  in  partheno- 
genic  animal  eggs,  407. 

Meganucleus:  division  of,  137;  behavior 
of,  in  endomixis,  143. 

Megaspore,  of  seed  plants,  320. 

Meristematic  tissue,  244,  246. 

Mesostomatidae,  susceptibility  of,  in 
relation  to  age,  loi. 

Metabolic  rate:  in  relation  to  age,  65, 
178,  183,  186,  271;  in  relation  to  sus- 
ceptibility, 66,  71,  72,  73.  79,  82; 
susceptibility  methods  of  comparing, 
73,  77,  82;  increase  in,  during  recon- 
stitution in  Planaria  dorotocephala, 
106;  increase  in,  during  reconstitution 
in  various  other  forms,  no;  increase 
in,  in  agamic  reproduction  in  infusoria, 
142;  increase  in,  during  starvation  in 
Planaria  dorotocephala,  156;  decrease 
in,  during  loading  of  pancreas  cell,  189; 
in  axial  gradients,  202,  243;  in  biaxial 
forms  of  Tiibularia,  211;  in  relation  to 
dominance,  216,  224;  in  relation  to 
position  of  parts,  222;  in  relation  to 
transmitted  changes,  225;  in  relation 
to  degree  of  individuation,  228;  in 
relation  to  physiological  isolation,  232; 


INDEX 


475 


in  relation  to  age  in  plants,  239,  243, 
246.  255;  in  relation  to  spore  formation 
in  plants,  248,  251;  in  nervous  system, 
267;  in  relation  to  body  surface,  271; 
in  relation  to  senile  atrophy,  287; 
during  starvation  in  man,  208;  during 
starvation  in  fishes,  300;  determined 
largely  by  internal  factors  in  warm- 
blooded animals,  303 ;  in  differentiation 
of  gametes,  349,  350,  351;  in  flower 
and  its  parts,  349,  374;  in  conjugating 
infusoria,  352,  380;  at  stage  of 
maturation,  355;  in  plant  at  time  of 
flowering,  375;  during  development  of 
flower,  375;  in  relation  to  gamete  for- 
mation in  hydra,  383;  in  germ  cells  of 
trematode  larvae,  396;  after  fertiliza- 
tion in  sea-urchin  and  starfish  eggs, 
405;  after  fertilization  in  annelids,  406; 
evidence  for  increase  of,  during  early 
embryonic  development  of  animals, 
411,  412;  in  larva  of  Nereis,  414; 
in  relation  to  nuclear  and  cytoplasmic, 
volume  during  early  development,  419. 
See  also  Metabolism;   Susceptibility. 

Metabolism:  chemical  conception  of,  14; 
Hober's  conception  of,  19;  physical, 
of  stream,  28;  production  of  water  in, 
37;  substratum  as  sediment  of,  41 ;  as 
a  reaction  system,  43;  change  in  char- 
acter of,  during  differentiation,  50;  in 
relation  to  narcotic  action,  67;  in- 
complete character  of,  435 ;  Kassowitz' 
theory  of,  442;  constructive,  in  relation 
to  nucleoplasmic  interchange,  444.  See 
also  Metabolic  rate;   Susceptibility. 

Metamorphosis,  larv'al:  in  Nereis,  421; 
in  Branchipiis,  422;  in  insects,  422; 
as  a  partial  physiological  disintegration 
of  individual,  423;    in  amphibia,  424. 

Metaplasm,  52,  439,  442.  See  also  Cell; 
Differentiation;     Protoplasm. 

Miastor,  germ  path  in,  328. 

Micronucleus:  division  of,  137;  behavior 
of,  in  endomixis,  143. 

Microspore,  of  seed  plants,  320. 

Mimiiliis  tilingii,  influence  of  light  on 
flowering  in,  371. 

Mnemiopsis  leidyi,  susceptibility  of,  in 
relation  to  age,  loi. 

Moniezia:  dedifferentiation  of  paren- 
chyme  cells  of,  258;   origin  of  gametes 

in,  331- 
Miicor:  spore  formation  in,  248;  gametes 
of,  316. 

Narcotic  action:  general  character  of,  66; 
theories  of,  67;  effect  of,  on  transmis- 
sion in  nerves,  218;  effect  of,  on  recon- 
stitution  in  Planaria  dorolocephala,  222. 


Ncplirodium,   archegonium   and   egg   of, 

338. 

.\  ercis:  a.xial  gradient  in  embryos  of,  203; 
susceptibility  of  eggs  of,  after  fertiliza- 
tion, 406.  414;  increase  in  suscepti- 
bility during  early  development  of. 
414;  metabolic  rate  in  larva  of,  414; 
period  of  developmental  rejuvenescence 
in,  compared  with  that  of  Arciiicolo, 
415;    segmentation  in  lar\-a  of,  421. 

Nervous  system:  of  Planaria  dorolo- 
cephala, 92;  structure  of,  in  relation 
to  degree  of  reconstitution  in  Planaria 
dorolocephala,  1 1 1 ;  in  relation  to  devel- 
opmental gradients,  205;  transmission 
in,  218,  227,  230;  in  relation  to  physio- 
logical integration,  224;  physiological 
stability  of,  281,  297;  water  content 
of,  in  relation  to  senescence,  2S3;  nu- 
cleoplasmic relation  in  cells  of,  during 
development,  284;  mor|)hological  age 
changes  in  cells  of,  287;  dedifferentia- 
tion in,  295;  rejuvenescence  in,  297; 
in  relation  to  death,  301. 

Normal  form,  in  reconstitution  of 
Planaria  dorolocephala,   iii. 

Nucleoplasmic  relation:  Minot's  views 
concerning,  284,  440;  in  development 
of  nerve  cells,  285;  in  early  embryonic 
development,  418;  R.  Hert wig's  views 
concerning,  439;  in  relation  to  senes- 
cence, 439. 

Nutrition:  Putter's  views  concerning, 
164;  character  of,  in  relation  to  age 
cycle,  169,  179,  276,  388;  difficulties  of 
experimental  control  of,  277;  effect  of 
qualitatively  inadequate,  278;  effect 
of  quantitatively  insufficient,  280; 
effect  of  excess  of,  298;  in  relation  to 
conjugation,  378;  in  relation  to  par- 
thenogenesis and  zygogencsis,  390, 
392,  408;  in  relation  to  surface  and 
volume,  438.  Sec  also  Reduction; 
Starvation. 

Ocdogonium:  conditions  of  spore  forma- 
tion in,  252;  gametes  of,  316. 

Oligochetes:  susceptibility  of.  in  relation 
to  age,  102;  increase  in  suscci)tibility 
of,  in  reconstitution,  no;  increase  in 
susceptibility  of.  in  agamic  reproduc- 
tion, 136;    axial  gradient  in.  203,  205. 

Oogenesis:  in  animals  in  general.  340; 
in  hydra,  340;  in  Fasciola  hepatica, 
340;  in  Pluwatella  jtingosa,  340;  in 
Sternaspis  scutata,  341;  in  Dytiscus 
marginalis,  342;  in  ascidian,  342; 
in  fish,  342;  in  Sida  cryslaJlina,  343; 
in  plant  lice.  344-  Src  also  (lamctc 
formation;  Gametes. 


476 


SENESCENCE  AND  REJUVENESCENCE 


Oogonium,  in  algae,  316. 

Organism:  neo-vitalistic  conception  of,  9; 
corpuscular  conception  of,  11;  com- 
pared with  crystal,  16,  199;  com- 
pared with  flame,  27;  compared  with 
flowing  stream,  27,  41,  58,  226;  com- 
pared with  machine,  29;  Huxley's 
conception  of,  41 ;  construction  of,  by 
function,  44.  See  also  Individual; 
Individuation. 

Oxidation:  in  relation  to  structure,  28; 
rate  of,  in  relation  to  growth,  43; 
effect  of  cyanides  and  narcotics  on,  66; 
decrease  in,  during  narcosis,  68,  71; 
rate  of,  in  young  and  old  parts  of  plants, 
239;  rate  of,  in  flower  and  its  parts, 
349,  374;  change  in  rate  of,  during 
development  of  flower,  375;  rate  of, 
after  maturation  and  fertilization  in 
sea-urchin  and  starfish,  405;  increase 
in  rate  of,  during  early  embr>-onic 
development  in  animals,  412.  See 
also  Metabolic  rate;   Metabolism. 

Oxygen  consumption:  decrease  of,  during 
narcosis,  68;  increase  of,  in  stimulated 
gland  cell,  189;  after  fertilization  in 
sea-urchin  and  starfish,  405;  during 
early  embryonic  development,  411. 
See  also  Oxidation. 

Paramecium:  agamic  breeding  of,  136; 
conjugation  in,  136;  agamic  reproduc- 
tion in,  137;  aurelia  a,nd caudatum,  138, 
143;  rejuvenescence  of,  in  agamic 
reproduction,  141;  endomixis  in,  143; 
effect  of  conjugation  in,  404. 

Parthenogenesis:  in  plants,  322  footnote  2, 
408;  in  bee,  345,  395;  in  relation  to 
zygogenesis  in  invertebrates,  389,  410; 
in  relation  to  physiological  age,  393, 
406;  in  relation  to  rate  of  egg  produc- 
tion, 394,  395,  408;  in  trematode 
larvae,  395;  artificial,  405;  resem- 
blance of,  to  agamic  and  experimental 
reproduction,  407;  conditions  deter- 
mining, 407;  "artificial,"  408;  grada- 
tions between,  and  zygogenesis,  410. 
See  also  Fertilization;  Gametes. 

Parthenogenic  egg:  oogenesis  of,  com- 
pared with  that  of  zygogenic  egg,  343: 
female-producing  and  male-producing, 
390;  younger  than  zygogenic  egg,  393, 
407,  410;  germ  cell  of  trematode  larva 
S'S,  39S;  general  characteristics  of,  408. 

Parthenogenic  female,  in  Crustacea,  390. 

Penicillium,  spore  formation  in,  248. 

Pennarla  tiarella:  susceptibility  of,  in 
relation  to  age,  loi;  agamic  reproduc- 
tion in,  148,  150;  rejuvenescence  of, 
in  agamic  reproduction,  149,  151. 


Periodicity:  in  organisms  in  general,  187, 
296,  297;  in  accumulation  of  carbon 
dioxide,  188;  in  fatigue  and  recovery, 
188,297;  in  pancreas  cell,  189,  296;  in 
plants,  191;  in  gametic  reproduction, 
192,  388;  in  growth,  276,  388;  in 
flowering,  375.  See  also  Age  cycle; 
Life  cycle. 

Permeability:  role  of,  in  organisms,  24; 
theories  of,  25;  in  relation  to  narcotic 
action,  69. 

Phagocata  gracilis,  susceptibility  of,  in 
relation  to  age,  loi. 

Phytoid,  237,  239. 

Plagiostomum  girardi,  axial  develop- 
mental gradients  in,  205. 

Planaria  dorotocephala:  reduction  of, 
during  starvation,  35,  157;  structure 
of,  92;  susceptibility  of,  in  relation  to 
age,  99;  reconstitution  of,  103;  change 
in  susceptibility  of  pieces  of,  after  sec- 
tion, 105;  reconstitution  of,  in  relation 
to  internal  and  external  factors,  in; 
degrees  of  reconstitution  of,  in; 
rejuvenescence  of,  in  experimental 
reproduction,  116;  rejuvenescence  of, 
in  repeated  reconstitution,  118;  agamic 
reproduction  of,  122;  act  of  fission  in, 
124;  prevention  of  fission  in,  125; 
rejuvenescence  of,  in  agamic  repro- 
duction, 126;  rejuvenescence  of ,  during 
starvation,  157;  rate  of  reduction  of, 
in  starvation,  162;  acclimation  of, 
during  starvation,  165;  axial  gradients 
in,  202;  dominance  and  subordination 
during  reconstitution  of,  213;  limit 
of  dominance  in  agamic  reproduction 
of,  221;  reconstitution  of,  in  narcotics, 
222;  spatial  factors  of  dominance  in, 
222;  conditions  of  gamete  formation 
in,  384. 

Planaria  maculata:  susceptibility  of,  in 
relation  to  age,  93;  time  not  a  measure 
of  age  in,  97;  agamic  reproduction  in, 
124;  rejuvenescence  of,  in  agamic 
reproduction,  126. 

Planaria  simplicissima,  biaxial  posterior 
ends  in,  215. 

Planaria  velata:  susceptibility  of,  in 
relation  to  age,  loi;  agamic  reproduc- 
tion of,  130,  169;  rejuvenescence  of, 
in  agamic  reproduction,  132;  inhibi- 
tion of  senescence  in,  165;  senescence 
of,  in  relation  to  character  of  nutrition, 
169;    involution  in,   171. 

Plumaklla  fungosa,  oogenesis  of,  340. 

Polarity,  physiological,  occurrence  of, 
200.  See  also  Axes:  Dominance; 
Individual;   Individuation. 


INDEX 


4/ 


Pollen  Rrain:  development  of,  320; 
rate  of  oxidation  in  development  of, 

349,  374- 

Polyembryony :  in  armadillo,  231,  269; 
in  insects,  268. 

Preformation,  46. 

Primitive  germ  cell.     See  Germ  path. 

Progression,  57.  See  also  Development; 
Differentiation;    Senescence. 

Protamine,  in  sperm  head,  353. 

Proteids:  occurrence  of,  in  organisms, 
14;  labile  molecule  of,  14,  19;  dis- 
tinction between  living  and  dead,  15; 
changes  in,  at  death,  16;  significance 
of,  for  life,  20;  molecular  constitution 
of,  20,  277;  colloid  character  of,  20; 
synthesis  of,  in  growth,  39,  278;  physio- 
logical stability  of,  39;  nutrition 
experiments  with  specific,  278;  changes 
in  proportional  amount  of,  during 
senescence,  283,  444;  in  differentiation 
of  sperm  head,  353.  See  also  Colloids; 
Stability,   physiological;     Substratum. 

Prothallium,  238,  245,  366. 

Protoplasm:  chemical  conception  of,  14; 
physico-chemical  character  of,  19; 
undifferentiated,  48,  51,  245;  changes 
in  aggregation  of,  50;  evolutionary 
senescence  of,  194,  464.  See  also 
Colloids;    Proteids;    Substratum. 

Protozoa:  agamic  reproduction  and 
rejuvenescence  in,  136;  division  in, 
137;  occurrence  of  death  in,  305.  See 
also  Infusoria. 

Radiate,  200. 

Reconstitution:  in  Planaria  dorolo- 
cephala,  103;  rejuvenescence  in,  107, 
no,  114,  116,  118.  180,  240;  in  rela- 
tion to  internal  and  external  factors, 
in;  degrees  of,  in;  repeated,  in 
Planaria  dorolocephala,  118;  resem- 
blance of,  to  agamic  reproduction,  126, 
132,  135,  140;  after  partial  involution 
in  Planaria  velala,  172;  termination  of, 
181;  origin  of  axial  gradient  in,  207; 
independence  of  apical  region  in,  210, 
213;  dominance  and  subordination  in, 
213,  215;  of  head  in  Planaria  dorolo- 
cephala, 215;  resemblance  of,  to  cmbr)'- 
onic  development,  215;  spatial  factor 
of  dominance  in,  222. 

Redifferentiation.  See  Dedifferentia- 
tion;  Development;  Senescence,  indi- 
vidual. 

Reduction:  definition  of,  34,  37;  chemical 
conception  of,  38;  during  starvation 
in  Planaria  dorotocepliala,  35,  44,  155; 
during  decreased  metaboHsm,  45;  after 
fragmentation  in  Planaria  velata,  131; 


of  cell  size  in  starvation,  155; 
variable  limit  of,  in  Planaria  doroto- 
cepliala, 156;  rate  of,  in  starvation  in 
Planaria  dorolocephala,  162;  of  bran- 
chial region  in  Clavellina,  2 58;  of  less 
stable  constituents  during  |)artial 
starvation,  281;  difference  between, 
and  atrophy,  288;  in  fishes,  300.  See 
also  Dedifferentiation;  Rejuvenescence. 

Regeneration  in  e.xcess,  43. 

Regression,  57,  155.  See  also  Dediffer- 
entiation; Reconstitution;  Reduc- 
tion; Rejuvenescence;  Reproduction; 
agamic,  gametic. 

Rejuvenescence:  occurrence  of,  in  gen- 
eral, 3,  4,  5,  8,  64,  178,  180,  chaps.  X. 
xii,  xv;  definition  of,  58;  general  char- 
acter of,  64,  186;  Maupas'  conclusions 
concerning,  64,  377,  434;  in  reconstitu- 
tion in  Planaria  dorolocephala,  107; 
in  reconstitution  in  other  forms,  no; 
degrees  of,  in  reconstitution,  n4,  iSo; 
degrees  of,  in  experimental  and  gametic 
reproduction,  116;  in  repeated  recon- 
stitution, 118;  in  agamic  reproduc- 
tion in  Planaria,  126;  in  agamic  re- 
production in  infusoria,  141,  378;  in 
relation  to  endomixis,  143;  in  agamic 
reproduction  in  hydra.  146;  in  agamic 
reproduction  in  Pcnnaria,  149,  151; 
in  star\-ation  in  Planaria,  157,  178; 
in  relation  to  acclimation  during  star\'a- 
tion,  165;  in  relation  to  character  of 
nutrition,  169;  in  relation  to  cell 
division,  182,  242;  in  relation  to 
gametic  reproduction,  186,  192,  270, 
chap.  XV,  434;  in  relation  to  other 
periodicities,  187,  296;  Braun's  ideas 
concerning,  237;  in  vegetative  life  of 
plants,  239;  in  plant  cell,  245;  in  siwre, 
252,  253;  in  agamic  repnKluction  in 
lower  animals,  255;  without  rei)ro<iuc- 
tion  in  lower  animals,  256;  morpho- 
logical evidence  for,  in  animals,  257, 
294;  as  result  of  senescence,  259; 
limitation  of.  in  higher  animals,  267, 
270;  after  hibernation,  290;  in  ner\'ous 
system,  297;  after  starvation  in  higher 
animals  and  man,  298;  after  loss  of 
weight  in  disease,  299;  during  star\'a- 
tion  in  fishes,  300;  after  starvation 
in  ami)hibia,  300;  in  translormalion 
of  flower  into  vegetative  shix)l,  377; 
in  different  races  of  Paramecium,  382; 
in  dai)hnid  Crustacea,  392.  304;  '" 
larval  life  history  of  digenctic  trcma- 
todes,  396;  e\idencc  for  occurrence 
of,  in  embryonic  development,  411. 
412;  period  of  developmental,  in 
Nereis  and  Arenicola,  41O;  degree  and 


478 


SENESCENCE  AND  REJUVENESCENCE 


period  of  developmental,  in   Tautogo- 
labrus  and  Funduhis,  417;    in  relation 
to  segmentation  in  Nereis  larva,  421; 
in  embryonic  development  of  plants, 
424;   degree  of,  in  agamic  and  gametic 
reproduction,  425;    by  substitution  of 
gametic,  for  agamic  reproduction,  426; 
as  a  casting  off  of  injurious  substances, 
435;    Minot's  theory  of,  441;    nucleo- 
plasmic  relation  in,  441;    as  result  of 
increase  in  nucleoplasmic  interchange, 
444;    in  relation   to   colloid    changes, 
445;     as   a   reversal   of   autocatalytic 
reaction,  448;    not  a  special  process, 
459;     not    necessarily    a    reversal    of 
senescence,    459;      possibility    of,    in 
evolution,  464;   in  non-living  systems, 
465.        See      also      Dedifierentiation; 
I\Ietabolic  rate. 
Reproduction,  agamic:   in  Planar  la  doro- 
toccphala,    122;     resemblance    of,    to 
reconstitution,  126,  132,  135,  140;    re- 
juvenescence in,  126, 141, 146, 149,  151, 
181,  239,  252,  255;   in  Planaria  vclala, 
130;    in  Stenostomum,   133;    in  oligo- 
chetes,  136;  in  infusoria,  137,  377,  379; 
in  hydra,  145;   limit  of  dominance  in, 
220;    in  plants,  221,  231,  238;    in  rela- 
tion to  physiological  isolation,  229;   in 
armadillo,  231;    different  forms  of,  in 
plants,  239,  247;    in  relation  to  indi- 
viduation in  plants,  244;    in  gameto- 
phyte    of    plants,    254,    366;     various 
forms  of,  in  lower  animals,   255;    as 
a    result    of    senescence,    259;     infre- 
quency    of,    in    higher    animals,    268; 
in  production  of  gametophyte,  377;   in 
relation  to  conjugation,  377;  in  marge- 
lid  medusa,  384;   degree  of  rejuvenes- 
cence in  gametic  and,  425.     See  also, 
Dedifferentiation;  Reconstitution;  Re- 
juvenescence;  Reproduction,  gametic, 
in  general. 
Reproduction,  experimental:  in  Planaria 
dorotocephala,     103,     105,     214,     222; 
ditierent  degrees  of,  in;  in  Tubularia, 
210;    continued,  in  plants,    239,  370. 
See   also    Reconstitution;     Rejuvenes- 
cence;   Reproduction,  agamic. 
Reproduction,  gametic:   absence  of,  99, 
130,  136,  239,  366,  369,  386,  387,  388; 
rejuvenescence  in,  186,  270;  periodic, 
192,   388;    prevention   of,  by   agamic 
reproduction,  239,  367,  370;  in  relation 
to    senescence,    270,    chap.    xiv,_  460; 
parthenogenic  and  zygogenic,  in  inver- 
tebrates, 389;  degree  of  rejuvenescence 
in  agamic  and,  425;  Godlewski's  com- 
parison   of,    with    regeneration,    427. 
See    also    Conjugation;     Fertilization; 


Gamete    formation;     Gametes;     Par- 
thenogenesis; Reproduction  in  general. 

Reproduction  in  general:  as  characteristic 
of  organism,  i,  202;  in  relation  to  age 
cycle,  178,  259;  different  processes  of, 
in  plants,  238,  247;  cycle  of,  in  inver- 
tebrates, 390;  fundamental  similarity 
of  all  forms  of,  427;  as  condition  of 
death  and  rejuvenescence,  433;  defini- 
tion of,  460;  inheritance  involved  in  all 
cases  of,  462.  See  also  Reconstitution; 
Rejuvenescence ;  Reproduction,  agamic, 
experimental,  gametic. 

Reproductive  cycle:  in  daphnid  Crus- 
tacea, 390;  repetition  of,  392;  in 
rotifers,  392;  in  trematodes,  395.  See 
also  Reproduction,  agamic,  experi- 
mental, gametic,  in  general. 

Reversibility:  of  reaction,  38,  56,  67,  71; 
of  development,  56,  64,  155,  188;  of 
relative  susceptibilities,  72,  82. 

Riccia,  origin  of  gametes  in,  318. 

Rotifers,  parthenogenesis  and  zygo- 
genesis  in,  392. 

Saggita,  germ  path  in,  328. 

Saprolegnia:  spore  formation  in,  247; 
conditions  of  spore  formation  in,  250; 
gametes  of,  316;  conditions  of  gamete 
formation  in,  364. 

Sea-urchin:  axial  gradient  in,  203; 
temperature  coefhcient  of  length  of 
life  in  eggs  of,  308;  susceptibility  of 
eggs  of,  351;  increase  in  metabolic 
rate  in  eggs  of,  after  fertilization,  405, 
414;  conditions  of  maturation  in,  405; 
oxygen  consumption  during  early 
development  of,  4";  heat  production 
during  early  development  of,  412; 
susceptibility  during  early  develop- 
ment of,  41 2 ;  critical  stage  in  develop- 
ment of,  413. 

Secretions,  internal.     See  Correlation. 

Segmentation:  in  higher  animals,  269; 
in  larva  of  Nereis,  421;  in  larva  of 
BranchipKS,  422. 

Segregation.  See  Gametes;  Germ  path; 
Germ  plasm. 

Self -differentiation:  in  general,  50,  55; 
of  apical  region  of  Tubularia,  210;  of 
apical  region  of  Planaria  dorotocephala, 
213. 

Sempervivum  funkii,  Klebs's  experiments 
on  control  of  flowering  in,  372. 

Senescence,  evolutionary:  occurrence  of, 
193,  464;  paleontological  evidence  for, 
193;  in  evolution  of  higher  organisms, 
464;  control  of,  465. 


INDEX 


479 


Senescence,    individual:     occurrence    of, 

in  organisms,  2,  178,  461;   significance 
of,  3;    definition  of,  58,   185;    general 
character  of,  63,  441;    morphological 
changes  during,  86,  284;    as  condition 
of  rejuvenescence,  133,  186,  259,  461; 
in  protozoa,   142,  379;    in  relation  to 
endomixis,  143;  in  relation  to  hydranth 
and  medusa  buds  in  Feniiaria,  151,  256; 
inhibition  of,  167,  239,  257,  279,  303; 
in  relation  to  character  of  nutrition, 
169,  276;    theories  of,  182,  chap,  xvi; 
changes  in  water  content  during,  184, 
279,  28s;    in  relation  to  other  periodi- 
cities, 1 8 7,  192,  296;   in  vegetative  life 
of  plants,  239;    in  whole  and  parts  of 
plants,  239,  241,  243;    in  growing  tips 
of  plants,    244;     in    relation   to  spore 
formation  in  plants,  251,  253;   as  con- 
dition of  specialized  agamic  reproduc- 
tion in  animals,   256;    in   absence  of 
growth,  282;   changes  in  chemical  con- 
stitution during,  283;   atrophy  in  later 
stages  of,  287,  301 ;  internal  determina- 
tion of  rate  of,  in  warm-blooded  ani- 
mals, 303 ;   in  development  of  gametes, 
349;    in  relation  to  maturation,  355; 
in    relation    to   gamete    formation    in 
algae  and  fungi,  364;    in  relation  to 
gamete  formation  in  mosses  and  ferns, 
366;     in    relation    to    flowering,    368; 
as  condition  of  conjugation,  378;    in 
different    races    of    Paramecium,  ^82; 
in    relation    to   gamete    formation    in 
hydra,    384;     in    relation    to    gamete 
formation   in   margelid   medusa,   384; 
in    relation    to   gamete    formation    in 
planarians,  384;   in  relation  to  gamete 
formation  in  other  invertebrates,  387; 
in    relation    to    gamete    formation    in 
vertebrates,  388;     in  relation  to  par- 
thenogenesis and  zygogenesis  in  inver- 
tebrates, 391,  392;   in  larval  life  cycle 
of  digenetic  trematodes,  396;  suscepti- 
bility in  early  development  in  relation 
to,  412;    larval  stages  and  metamor- 
phosis in  relation  to,  420;  as  a  wearing 
out,  433;    as  an  adaptation,  433;    as 
result  of  reproduction,  433;    as  result 
of    atrophy    of    sex    organs,    434;     as 
result  of  inhibition  of  growth  impulse, 
434;   as  an  intoxication,  434;   as  result 
of  organic  constitution,  436;  in  relation 
to  surface  and  volume,  437;  as  result  of 
starvation  of  cells,  437;   nucleoplasmic 
relation  in,  439;    in  relation  to  cyto- 
morphosis,  440;  as  result  of  dilTerentia- 
tion,  442;   as  result  of  accumulation  of 
metaplasm,  443 ;  in  relation  to  decrease 
of  assimilatory  capacity,  444;    "dilu- 


tion"   of   nitrogen    in    pianis   during, 
444,    453;     as    result    of   decrease    in 
nucleoplasmic    interchange.    444;     in 
relation   to   colloid   changes,   445;    as 
retardation  of  an   autotalalvlic   reac- 
tion by  accumulation  of  |)ro<Jucls,  448; 
not   a   special   process,   459;     in    non- 
living   systems,    465.     Sa-    also    Age; 
Age  cycle;   Development;   Differentia- 
tion;  Senescence,  evolulionarv,  racial. 
Senescence,  racial:   in  protozoa,  136,  378; 
in    relation    to    endomixis,    143;     in 
Planaria  vclala,   173,   179;    in  relation 
to    conjugation,    378,    383,    434;     in 
relation  to  parthenogenesis  and  zygo- 
genesis    in     invertebrates,     390;      in 
potato,  426;   conditions  of,  42O,  561. 
Senility:     atrophy   as   characteristic   of, 
2S7,   301;     rnori)hoIogical   changes  in, 
287;  as  a  "wearing  out"  of  physiologi- 
cal mechanism,  288,  433;   mental.  297; 
in  relation  to  fatigue  and  exhaustion. 
297;  as  result  of  atrophy  of  sex  organs. 
434;   as  result  of  sjjecial  conditions  not 
connected  with  growth,  448.     See  also 
Death;     Differentiation;     Senescence; 
individual. 
Sida  crystalliiia,  oogenesis  of,  343. 
Silphium,  pollen  grain  and  spermatozoid 

of,  334- 
Specification,  46. 
Spermatogenesis,  in  guinea-pig,  335.     See 

also  Gamete  formation;    Gametes. 
Spermatogenous   cell,   segregation    of,  in 
plants,    318,    320.     See    also    Gamete 
formation;  Gametes. 
Spermatozoid    of    plants.     See    Gamete 

formation;  Gametes. 
Spermatozoon  of  animals.     Sec  Fertiliza- 
tion; Gamete  formation;  Gametes. 
Spirogyra,  gametic  reproduction  in,  316. 
Sporangium,  247,  250. 
Spore  formation:  in  plants,  233,  238,  241, 
247;    in   relation   to  senescence,    241. 
248;    rejuvenescence  in,  252,  253;    in 
relation  to  age  cycle  in  plants,   254; 
in  protozoa,  255. 
Sporophore,  248. 

Sporophyte:  in  relation  to  age  cycle,  253; 
in  mosses  and  ferns,  253;  origin  of,  in 
apogamy,  2,2^- 
Stability,  physiological:  nature  of.  35.  30; 
different  degrees  of.  41;  in  relation  to 
starvation,  44;  increase  in,  tluring 
development.  50,  183,  463;  in  relation 
to  metabolic  rate,  51,  279;  in  relation 
to  evolution.  53.  194,  267.  208,  304, 
460.  463;  in  relation  to  in<li\  idualion. 
227;  increase  in,  during  partial  slar\a. 
tion,  280,  282;    of  skeletal  substance- 


48o 


SENESCENCE  AND  REJUVENESCENCE 


281;  of  nervous  system,  281,  297;  of 
flower,  375;  in  animal  egg,  407.  See 
also  Dedifferentiation;  Differentiation; 
Substratum. 
Starfish:  axial  relations  in,  200;  axial  gra- 
dient in,  203;  early  death  after  matur- 
ation of  unfertilized  egg  of,  307,  405; 
susceptibility  of  eggs  of,  351,  413; 
oxygen  consumption  in  egg  of,  in  rela- 
tion to  fertilization,  405,  414;  condi- 
tions of  maturation  in,  405;  egg  of, 
almost  parthenogenic,  405,  410;  suc- 
ceptibility  during  early  development 
of,  413;   critical  stage  in  development 

of,  413- 
Star\^ation:  in  Planar ia  dorotocephala, 
35,  155,  156;  reduction  of  nervous 
svstem  during,  35,  281;  in  other 
p'lanarians,  44;  decrease  in  cell  size 
during,  155;  death  from,  156;  inCassjo- 
pea,  163;  capacity  for  acclimation 
during,  165;  effect  of  partial,  167, 
280,  386;  stunting  effect  of  partial,  in 
mammals,  281;  rejuvenescence  in  con- 
nection with,  in  higher  animals  and 
man,  298,  299;  increase  in  weight 
after,  298,  300;  susceptibility  of  fishes 
during,  299;  senescence  as  a  process 
of  cell,  437.  See  also  Nutrition; 
Reduction;  Rejuvenescence. 
Statoblasts   of   bryozoa,   in   relation    to 

age  cycle,  256,  259. 
Stenostomum,    agamic    reproduction    in, 
133;    increase  of  susceptibility  during 
agamic  reproduction  in,  135. 
Stentor   coeruleus:     agamic   reproduction 
in,  138;    rejuvenescence  of,  in  agamic 
reproduction,  141,   142. 
Sternaspis  scutata,  oogenesis  of,  341. 
Strongylocentrotus     lividus,     increase     in 
oxygen  consumption  of,  during  early 
development,  405.   See  also  Sea-urchin. 
Subordination,  215. 

Substratum:  in  relation  to  reaction,  19, 
42;  physiological  stability  of,  40,  41  > 
50,  53,  183,  194,  227,  267,  298,  304, 
460,  463;  as  metabolic  sediment,  41; 
Huxley's  conception  of,  41;  function 
in  relation  to,  42;  selective  action^  of 
starvation  upon,  44;  changes  in,  during 
development,  45,  5°,  1^35  embry- 
onic cell  as  metabolic,  49;  action  of 
narcotics  on,  69,  70;  in  relation  to 
maintenance  of  axial  gradients,  226. 
See  also  Dedifferentiation;  Differentia- 
tion; Stability,  physiological. 
Summer  egg,  390. 

Surface  and  volume:   in  relation  to  nar- 
cotic  action,    75,    78;    in   relation   to 


metabolic    rate,    272;     in    relation    to 
senescence,  437;    significance  of  rela- 
tion between,  438. 
Susceptibility:  to  cyanides  and  narcotics, 
66;    in  relation  to  metabolic  rate,  66, 
71,  72,  73,  79,  82;   methods  of  use  of, 
73,    77,    82;     in    relation    to    carbon- 
dioxide  production,  73;    in  relation  to 
age     in    Planar  ia    maculata,    93;    in 
relation    to    age    in    Planaria    doroto- 
cephala,   99;     in    relation    to    age    in 
Planaria  velata,  loi;  in  relation  to  age 
in    other    forms,    loi;     of    pieces    of 
Planaria    dorotocephala    after    section, 
105;   in  relation  to  different  degrees  of 
reconstitution,    113;     increase    of,    in 
agamic  reproduction  in  Planaria  doro- 
tocephala and  P.  macidata,  127;  increase 
of,  in  agamic  reproduction  in  Planaria 
velata,    132;     increase    of,    in    agamic 
reproduction     in     Stenostomum,^  135; 
increase  of,  in  agamic  reproduction  in 
oligochetes,  136;  increase  of,  in  agarnic 
reproduction    in    infusoria,    141;     in- 
crease   of,    in     agamic    reproduction 
in  hydra,  146;    increase  of,  in  agamic 
reproduction   in   Pennaria,    149,    151; 
increase     of,     during     starvation     in 
Planaria  dorotocephala,   157;    in  rela- 
tion to  acclimation  in  starved  Planaria 
dorotocephala,     165;      in     relation     to 
axial    gradients,    202;     of  _  dominant 
region    to    external    conditions,    226; 
of   fishes   during   starvation,    299;    of 
gametes  of  animals,  351;    at  time  of 
conjugation,    352,    381;     of    sexually 
mature    Planaria    dorotocephala,    385; 
of  sexually  mature  Planaria  macidata, 
386;     of    different   larval   generations 
in  trematodes,  396;    increase  of,  after 
fertilization  in  animal  eggs,  405,  406; 
of    different    eggs    to    parthenogenic 
agents,  410;    of  starfish  during  early 
development,  413;   of  sea-urchin  dur- 
ing early  development,  413;   of  Nereis 
during    early    development,    414;     of 
Arenicola   during   early   development, 
415;    of  frog  and  salamander  during 
early     development,     418.     See     also 
Metabolic  rate. 
Symmetry,  physiological:   occurrence  of, 
201,  203;  in'relation  to  axial  gradients, 
204. 

Tautogolabrus  adspersus:  susceptibility 
of  eggs  of,  351:  susceptibility  during 
early  development  of,  416,  417;  period 
of  developmental  rejuvenescence  in, 
compared  with  that  in  Fundultis, 
417. 


• 


INDEX 


48 1 


Teleology:  the  problem  of,  30;  in  inter- 
pretation of  reduction  in  planarians, 
44;  in  interpretation  of  budding  in 
plants,  231;  in  interpretation  of  re- 
lation between  agamic  and  gametic 
reproduction  in  i)lants,  367,  369. 

Temperature  coeflicient:  of  rate  of 
chemical  reaction,  68;  of  length  of  life 
of  Planaria  doroloccphala  in  cyanides 
and  narcotics,  68;  of  length  of  life  of 
sea-urchin  eggs,  308;  of  rate  of  develop- 
ment, 308. 

Teratomorphic  form,  in  Planaria  dorolo- 
cephala,  in,  223. 

Teratophthalmic  form,  in  Planaria  doro- 
loccphala, III. 

Torreya  iaxifolia,  archegonium  and  egg 

of,  339- 

Transmission:  in  relation  to  colloids,  26; 
in  relation  to  axial  gradients,  209; 
decrement  in,  209,  217,  227;  as  means 
of  physiological  correlation,  217;  limit 
of,  217,  219,  231;  in  nerves,  218,  230; 
quantitative  effect  of,  225;  efficiency 
of,  227.  See  also  Conducting  paths; 
Conductivity. 

Trematode,  parthenogenesis  in  larvae 
of  digenetic,  395. 

Tubiilaria:  simple  individual  of,  210; 
reconstitution  of,  210;  limit  of  domi- 
nance in  agamic  reproduction  of,  220; 
limit  of  dominance  in  reconstitution 
of,  221. 


i'lollirix,  spore  formation  in,  247. 
Uroccnlrum     turbo,     rejuvenescence     of, 
in  agamic  reproduction,  141,  142. 

Vacuole,  in  infusoria,  137. 
Vacuolization,     in     plant     cells     during 

dilTerentiation,  245,  284. 
Vauchcria:     spore     formation     in,    247: 

conditions  of  spore  formation  in,  250; 

conditions    of    gamete    formation    in, 

365. 
Volume  and  surface.    See  Surface. 
Volvox,  gametes  of,  316. 

Water:  in  relation  to  colloids,  24;  in 
relation  to  growth,  36;  production  of, 
in  metabolism  37;  in  relation  to  senes- 
cence, 184,  279,  283. 

Winter  egg,  390,  404. 

Zamia:  spermatozoidof,334;  egg  of.  339. 

Zooid:  formation  of,  in  Planaria  doroto- 
cepliala,  123;  formation  of,  in  Stcno- 
stomitm,  133;  as  member  of  animal 
colony,  237. 

Zoospore,  247,  252. 

Zygogenesis,  343,  389;  gradations  be- 
tween, and  parthenogenesis,  410. 

Zygogenic  egg:  oogenesis  of,  compared 
with  that  of  parthenogenic  egg,  343; 
in  daphnid  Crustacea,  390. 

Zygospore,  in  algae  and  fungi,  316. 


Property  OT 

N.C.  COLLEGE  OF  AGRICULTURE 

Department  of  Zoology  and  Entomology 

Nc. „ 


Property  of 

N-  C.  COLLEGE  OF  AGRICULTURE 
Ceparln,ent  of  Zoology  and  Eniomology 
No 


North  Carolina  State  University  Libraries 

QH531  .C5 

SENESCENCE  AND  REJUVENESCENCE 


S02776454  K 


